The original cast consisted of Anthony Edwards as Dr. Mark Greene, George Clooney as Dr. Doug Ross, Sherry Stringfield as Dr. Susan Lewis, Noah Wyle as John Carter, and Eriq La Salle as Dr. Peter Benton. Julianna Margulies guest starred in the pilot as Carol Hathaway before becoming part of the regular cast. The first additions to the cast came in Season Two with Jeannie Boulet (Gloria Ruben) and Kerry Weaver (Laura Innes) signing on.
The cast remained largely unchanged until Season Five, when Kellie Martin joined the cast as medical student Lucy Knight and George Clooney became the first major departure.
As a result, Season Six opened with addition of then-unknown Croatian actor Goran Visnjic to the cast as the tragic Dr. Luka Kovac and soon after, Maura Tierney as Abby Lockhart, who together formed the series longest running, and most complicated, romantic relationship. By the end of Season 8, only two members of the original cast, Noah Wyle & Sherry Stringfield, remained.
|Actor||Role||Appearance as Star||as Guest Star / Supporting Actor|
|Anthony Edwards||Mark Greene||1–8, 15||1–179, 316|
|George Clooney||Doug Ross||1–5, 15||1–106, 328||6||134|
|Sherry Stringfield||Susan Lewis||1–3, 8–12, 15||1–55, 161–246, 331|
|Noah Wyle||John Carter||1–11, 15||1–245, 325-328, 331||12||259–260, 264–265|
|Eriq La Salle||Peter Benton||1–8, 15||1–167, 172, 178, 328, 331|
|Julianna Margulies||Carol Hathaway||1–6, 15||2-134, 328||1||1|
|Gloria Reuben||Jeanie Boulet||2–6, 14||31–119||1, 2, 14||14–17, 20–28, 301|
|Laura Innes||Kerry Weaver||3–13, 15||48–280, 331||2, 15||26–29, 31, 34–35, 38, 40, 43–47, 316|
|Maria Bello||Anna Del Amico||4||70–91||3||67–69|
|Alex Kingston||Elizabeth Corday||4–11, 15||70–227, 331||15||321, 331|
|Kellie Martin||Lucy Knight||5–6||92–127|
|Paul McCrane||Robert Romano||6–10||114–209||4, 5, 15||74–75, 77–81, 84–90, 93, 95–96, 100–101, 103–107, 109–113, 316|
|Goran Višnjić||Luka Kovač||6–15||114–290; 295, 298–300, 304, 306, 309, 312|
|Michael Michele||Cleo Finch||6–8||114–167, 178|
|Erik Palladino||Dave Malucci||6–8||120–161||6||115–119|
|Ming-Na||Jing-Mei Chen||6–11||123–232||1||13–17, 19–21|
|Maura Tierney||Abby Lockhart||6–15||125–310, 312||6, 15||121, 329|
|Sharif Atkins||Michael Gallant||8–10||172–219||8, 11–12||164–166, 168–170, 239–240, 253–254, 257, 266|
|Mekhi Phifer||Gregory Pratt||9–15||180–310||8||175–177, 179|
|Parminder Nagra||Neela Rasgotra||10–||204–331||10||202|
|Linda Cardellini||Samantha Taggart||10–||206–331|
|Shane West||Ray Barnett||11–13||224–290||15||314, 329-330|
|Scott Grimes||Archie Morris||12–||246–331||10–11||204–206, 208–209, 212, 215–217, 220–222, 224, 226, 228, 230, 232, 234, 236, 238–239, 241–242, 244–245|
|John Stamos||Tony Gates||13–||269–331||12||252–253|
|David Lyons||Simon Brenner||15||310–331||14||304, 306-309|
|Angela Bassett||Cate Banfield||15||311–331|
Main cast departures
Sherry Stringfield's first departure on the show was in 1996, when her character, Susan Lewis, moved to Phoenix, Arizona, in the Season 3 episode "Union Station." In 2001, Stringfield returned to the series, reprising her role of Dr. Lewis, in the Season 8 episode "Never Say Never." She departed again in the Season 12 premiere, "Canon City." This second departure was not depicted, but rather mentioned by character Kerry Weaver four episodes later in "Wake Up," when she explains that Susan had accepted a tenure-track position at a hospital in Iowa City, Iowa, after having been denied tenure at County. She is set to appear on one episode of the 15th. and final season.
After playing Anna Del Amico for one season, Maria Bello was not a part of the ensemble cast when Season 5 began. Like Susan Lewis's second exit, her character's departure was mentioned but not depicted; in the season premiere, "Day for Knight," Carter explains to new medical student Lucy Knight that the locker she is inheriting used to belong to Anna Del Amico, who is working in a pediatric ER back in Philadelphia, where she has family and a boyfriend.
George Clooney left the show in 1999, in the Season 5 episode "The Storm, Part 2," when his character, Doug Ross, quit before being fired by County for his involvement in a patient's death. Clooney made a brief reappearance in the Season 6 episode "Such Sweet Sorrow" when his character reunited with Carol Hathaway. He and Margulies are returning for one last episode of ER's 15th and final season.
Gloria Reuben departed early in Season 6, in the episode "The Peace of Wild Things," when her character, Jeanie Boulet, decided to become a stay-at-home mom and care for her newly adopted HIV-positive baby. She returned in season 14 for one episode with her HIV positive child.
Kellie Martin, who played medical student Lucy Knight, left the series midway through Season 6 in the episode "All In The Family," when her character was killed by a patient suffering from undiagnosed schizophrenia; his psychotic break occurred before a backed-up psychiatry department could arrive in the ER for a consult.
Julianna Margulies left the show at the end of Season 6, in the episode "Such Sweet Sorrow," when her character, Carol Hathaway, decided on the spur of the moment to go to Seattle, Washington, and reunite with Doug Ross, her true love and the father of her twin daughters. She and George Clooney are returning for one last episode of ER's 15th and final season.
Eriq La Salle's character, Peter Benton, departed in the Season 8 episode "I'll Be Home For Christmas". He took a job with a set schedule at another hospital in order to spend more time with his son, Reese, and his girlfriend, former fellow ER doctor Cleo Finch. His character returned two more times that season in episodes "It's All In Your Head" and "On The Beach". He is returning one last time during Season 15 in episode "Old Times" when Benton visits a hospitalizied Carter.
Michael Michele's character, Cleo Finch, departed in the Season 8 episode "I'll Be Home For Christmas" with her boyfriend, and fellow doctor, Peter Benton, after having previously taken a job at the same hospital with set schedules (in fact it was she who arranged the interview which resulted in Benton's job offer). Her character returned one more time that season in the episode "On The Beach".
Anthony Edwards's character, Mark Greene, died of a brain tumor in Season 8's penultimate episode, "On the Beach." Unusually, Anthony Edwards was credited in the following episode "Lockdown". Edwards returned during the 15th and final season starring as Greene in episode "Heal Thyself". He appear in multiple flashback scenes to give insight into the past of Angela Bassett's character.
Paul McCrane's character, Robert Romano, whose arm had been severed just above the elbow by a helicopter's tail rotor in the Season 9 premiere "Chaos Theory," was killed in the Season 10 episode "Freefall" when a helicopter that was taking off from the hospital roof was buffeted by strong winds, causing it to crash on the roof and plummet over the side of the building; it fell into a crowded ambulance bay and landed squarely on Romano. He made an appearance on a flashback sequence during Season 15 episode "Heal Thyself".
Sharif Atkins left the series twice. The first time was in the Season 10 episode "Where There's Smoke," when his character, Michael Gallant, revealed that the Army was sending him to Iraq. He returned for two episodes in Season 11 and for four episodes in Season 12, where in the episode "The Gallant Hero and The Tragic Victor," he was killed by an improvised explosive device while serving a second tour in Iraq.
Alex Kingston's character, Elizabeth Corday, left the series in the Season 11 episode "Fear" after getting in trouble for performing an illegal organ donation procedure; rather than being summarily fired, County offered her a demotion to a non-tenured position, but she turned it down and opted to return to England instead. In an interview with Britain's Radio Times magazine, Kingston spoke of being written off the show due to her age, a statement that sparked some controversy. She later withdrew that claim. Kingston returned for an appearance for the show's final season in episode "Dream Runner".
Ming-Na left in Season 11 as an attending physician when her character, Jing-Mei Chen, resigned in in order to take care of her ailing father, whom she later euthanized in the episode "Twas the Night." This was the second time her character left County General; in Season 1, medical student "Deb" Chen recurred in an eight episode story arc which concluded with her leaving medical school after deciding she was better suited to research than to applied medicine.
Noah Wyle left in the Season 11 finale, "The Show Must Go On." His character, John Carter, after having received tenure at County, decided to reunite with his girlfriend Kem Likasu (portrayed by Thandie Newton). During Season 12, Wyle returned as Carter and made guest appearances in four episodes: "Quintessence of Dust," "Darfur," "No Place to Hide," and "There Are No Angels Here". On Season 15, Wyle returns once more as Carter to star in five of the last seven episodes: "The Beginning of the End", "T-Minus 6", "What We Do", "Old Times" and the series finale, "And in the End...".
Laura Innes left midway through Season 13, in the episode "A House Divided," when a reluctant Luka Kovač was forced by budget cuts to fire her character, Kerry Weaver. After bracing for a battle to keep her position, and in spite of the fact that Kovač realized he must find a way to keep her on staff, Weaver ultimately decided to resign from County and accept a job offer from a television station in Miami, Florida. She made an appearance on a flashback sequence during Season 15 episode "Heal Thyself".
Shane West left at the end of the 13th season after his character, Ray Barnett lost both his legs and returned to Baton Rouge with his mother to recuperate. West's final appearance as a main cast member was in "The Honeymoon is Over." He returned in the fifth episode of Season 15 entitled "Haunted" to visit Neela and the rest of the staff, and later in the twentieth, "Shifting Equilibrium".
Mekhi Phifer departed during the first episode of Season 15. His character, Gregory Pratt, died in the ER as the result of blast injuries suffered in an ambulance explosion in the final episode of Season 14.
Goran Višnjić departed in the third episode of season 15 in an episode entitled "Book of Abby" with his TV wife Abby Lockhart. Along with their son Joe, they presumably headed to Boston, where Abby got a new job.  Luka had previously left the show in the season finale of season 13 when he left for Croatia to care for his ailing father. He returned for seven episodes in season 14 to wrap up his medical storyline and then made a brief appearance in "Book of Abby" where he, Abby, and their son Joe embark on their new life together.
Maura Tierney departed in the third episode of season 15 in an episode entitled "Book of Abby" with her TV husband Luka Kovac. Along with their son Joe, they presumably headed to Boston, where Abby got a new job.  She attempted to leave the ER quietly, however the rest of the staff made it known how much they will miss her. Nurse Haleh Adams showed Abby a hidden wall with the locker labels of all the past staff members since season one, with the exception of Carter who refused to deface government property (the other names on the wall were mostly departed former characters as well as some prominent writers and producers). Abby then left the ER and met Luka and her son Joe outside where they embark on their new life together.