Chicago Medical Center is the main hospital in Chicago and is also the main setting of crossovers.
- Dr. William Halstead is the first-year Emergency Medicine attending.
- Dr. Ethan Choi is a Chief Resident in the Emergency Department.
- Dr. Connor Rhodes is one of the main Trauma Surgeons and is one of the newest, with Will and Jeff.
- Dr. Daniel Charles is the head of the Psychiatric Department, with his trainee Sarah Reese who he recruited after she quit Pathology in season 1.
- Dr. Natalie Manning
- Dr. Isidore Latham is one of the best Trauma Surgeon in the hospital.
- Dr. Sam Abrams
- April Sexton - nurse and sister of Noah Sexton, a first-year resident and trainee.
- Maggie Lockwood, nurse in charge of the Emergency Department and A&E, which she has named Baghdad.
- Dr. Robyn Charles - daughter of Dr. Charles and an epidemiologist.
- Dr. Nina Shores