- Doctors and Medical students
- William H. Macy as Dr. David Morgenstern – Chief of Surgery and Chief of Emergency Medicine
- Sam Anderson as Dr. Jack Kayson – Chief of Cardiology
- John Aylward as Dr. Donald Anspaugh – Chief of Staff
- CCH Pounder as Dr. Angela Hicks – Surgical Attending Physician
- Paul McCrane as Dr. Robert Romano – Surgical Attending Physician
- Jorja Fox as Dr. Maggie Doyle – Resident PGY-2
- David Brisbin as Dr. Alexander Babcock – Anesthesiologist
- Clancy Brown as Dr. Ellis West – Associate ER Attending Physician
- Michael Buchman Silver as Dr. Paul Meyers – Psychiatrist
- Matthew Glave as Dr. Dale Edson – Resident PGY-2
- Chad Lowe as George Henry – Medical Student
- Don Perry as Dr. Sam Breedlove – Surgeon
- Megan Cole as Dr. Alice Upton – Pathologist
- Ted Rooney as Dr. Tabash – Neonatologist
- Perry Anzilotti as Dr. Ed – Anesthesiologist
- Kenneth Alan Williams as Dr. Thomas Gabriel
- Alice Amter as Dr. Miriam Nagarvala
- Kenneth Tigar as Dr. Keinholz
- Kathleen Lloyd as Dr. Mack
- Dennis Boutsikaris as Dr. David Kotlowitz
- Justin Henry as James Sasser – Medical Student
- Joel de la Fuente as Ivan Fu – Medical Student
- Nurses
- Ellen Crawford as Nurse Lydia Wright
- Conni Marie Brazelton as Nurse Conni Oligario
- Deezer D as Nurse Malik McGrath
- Laura Cerón as Nurse Chuny Marquez
- Yvette Freeman as Nurse Haleh Adams
- Lily Mariye as Nurse Lily Jarvik
- Gedde Watanabe as Nurse Yosh Takata
- Dinah Lenney as Nurse Shirley
- Kyle Richards as Nurse Dori Kerns
- Bellina Logan as Nurse Kit
- Suzanne Carney as OR Nurse Janet
- Tricia Dong as Nurse Joyce
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- Staff, Paramedics and Officers
- Abraham Benrubi as Desk Clerk Jerry Markovic
- Mariska Hargitay as Desk Clerk Cynthia Hooper
- Kristin Minter as Desk Clerk Miranda "Randi" Fronczak
- Erica Gimpel as Social Worker Adele Newman
- Christine Healy as Hospital Administrator Harriet Spooner
- George Eads as Paramedic Greg Powell
- Emily Wagner as Paramedic Doris Pickman
- Montae Russell as Paramedic Dwight Zadro
- Lyn Alicia Henderson as Paramedic Pamela Olbes
- Brian Lester as Paramedic Brian Dumar
- J.P. Hubbell as Paramedic Lars Audia
- Claudine Claudio as Paramedic Silva
- Ed Lauter as Fire Captain Dannaker
- Mike Genovese as Officer Al Grabarsky
- Family
- Christine Harnos as Jennifer "Jenn" Greene
- Yvonne Zima as Rachel Greene
- Bonnie Bartlett as Ruth Greene
- John Cullum as David Greene
- Jonathan Scarfe as Chase Carter
- Frances Sternhagen as Millicent Carter
- George Plimpton as Grandpa Carter
- Michael Beach as Al Boulet
- Khandi Alexander as Jackie Robbins
- Taraji P. Henson as Patrice Robbins
- Mark Dakota Robinson as Steven Robbins
- Lisa Nicole Carson as Carla Reece
- Victor Williams as Roger McGrath
- Rose Gregorio as Helen Hathaway
- Trevor Morgan as Scott Anspaugh
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