In June 2020, Ben Whishaw joined the cast in the lead role of Adam Kay. Whishaw's casting was met with unanimous approval from the networks involved in the project. Controller of BBC Drama, Wenger said it was "a testament to the quality" of scripts that Whishaw had signed up. McDermott, co-president of AMC Studios was "thrilled" to secure an "established talent". Early on, Ambika Mod had signed up to play Shruti Acharya, a junior doctor (SHO) in obstetrics and gynaecology. Mod received the first scripts for the role in mid-2020. She recalled that upon reading through the first episode, Mod felt as though the role was "meant" for her. In June 2021, the casting details of the remainder of main roles in the series were announced. These castings consisted of hospital staff and Adam's personal relations. Michele Austin was cast as a sharp-witted midwife called Tracy, Kadiff Kirwan plays Julian who is Adam's rival work colleague, Ashley McGuire appears as consultant Vicky Houghton and Alex Jennings as consultant Nigel Lockhart who is Adam's boss. The casting of Adam's relatives included his boyfriend Harry Muir played by Rory Fleck Byrne, Harriet Walter as Adam's mother Veronique and Tom Durant-Pritchard as his best friend Greg.
