Clooney played pediatrician Doug Ross from seasons 1 through 5 and returned as a guest in seasons 6 and 15.

ER helped move him from television regular to film lead. , and producing through Smokehouse Pictures.

Edwards anchored seasons 1 through 8 as Mark Greene and returned through archival or special material later. The character's growth from senior resident to department leader made him the early series' institutional center.

Edwards later appeared in Zodiac, Inventing Anna, WeCrashed, and The Walking Dead: Dead City and continued stage and charitable work.

Wyle appeared from the pilot through season 11, returned in seasons 12 and 15, and let viewers watch Carter progress from medical student to experienced physician.

Later he led Falling Skies and The Librarians. In 2025 he returned to medical drama as Dr. Michael Robinavitch in The Pitt, also serving as an executive producer.

Margulies played nurse Carol Hathaway from seasons 1 through 6 and returned in the final season. She won an Emmy for the role, then later led The Good Wife and appeared in The Morning Show.

Her career shifted from ensemble medical drama to legal and newsroom authority while retaining the controlled emotional detail visible in Carol.

Stringfield played Susan in seasons 1 through 3, returned for seasons 8 through 12, and appeared in the finale.

Her departures and returns made Susan one of ER's earliest examples of a doctor whose career continued beyond what viewers saw. Later credits include Under the Dome, Criminal Minds: Beyond Borders, and recurring television work.

La Salle portrayed surgeon Peter Benton from seasons 1 through 8 and returned for season 15. D. and The Equalizer, while continuing to act and write novels.

Benton's precision foreshadowed a public career increasingly defined by decisions behind the camera.

Reuben played physician assistant Jeanie from seasons 1 through 6 and returned in season 14. The role brought early prime-time attention to a professional living with HIV without making diagnosis her only identity.

Reuben later appeared in Lincoln, Mr. Robot, City on a Hill, and Elsbeth and continued music and public-health advocacy.

Innes joined in season 2 as Kerry Weaver and remained through season 13, with a finale return. She also directed multiple ER episodes and built a directing career across The West Wing, How to Get Away with Murder, and other dramas.

The public record shows creative authority behind the camera as well as Weaver's authority within County General.

Kingston joined in season 4 as British surgeon Elizabeth Corday and stayed through season 11, returning for the final season.

She later became widely known as River Song in Doctor Who and appeared in Arrow, A Discovery of Witches, and stage productions. Her career links two major television institutions without reducing either role to the other.

Višnjić joined in season 6 as Croatian physician Luka and remained a regular through season 13, with later guest appearances. Subsequent credits include Red Widow, Extant, Timeless, The Boys, and Vikings: Valhalla.

His post-ER work has moved among science fiction, thriller, and historical drama while drawing on an international screen career.

Tierney entered in season 6 as nurse and medical student Abby, became a physician, and stayed through season 15.

She later won a Golden Globe for The Affair and appeared in Beautiful Boy, The Report, American Rust, The Iron Claw, and Twisters. The role's long training arc preceded a run of complicated adult drama performances.

Phifer joined in season 8 as emergency physician Gregory Pratt and remained through season 15. Before ER he had appeared in Clockers and 8 Mile; later work includes Lie to Me, Divergent, Truth Be Told, and Love, Victor.

Pratt's growth from confident newcomer to department leader gave the later seasons a durable professional arc.

Nagra joined in season 10 as medical graduate Neela and stayed through the finale, eventually specializing in surgery. Bend It Like Beckham had already introduced her internationally.

Later roles include Alcatraz, The Blacklist, 13 Reasons Why, Fortitude, and DI Ray, where she moved from ensemble doctor to police-drama lead.

Cardellini joined in season 10 as nurse Sam and remained through season 15. She had already starred in Freaks and Geeks and Scooby-Doo; later credits include Mad Men, Bloodline, the Avengers films, Dead to Me, and No Good Deed.

Her résumé moves easily between comedy, family mystery, thriller, and large franchise ensembles.

Grimes joined in season 10 as physician Archie Morris and developed from comic irritant into a senior emergency-department figure by season 15.

, The Orville, Oppenheimer, and music. Voice performance, science-fiction ensemble acting, and film roles have kept his post-ER career unusually varied.