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The biggest change to the show for the ninth season is a major cast revamp.

Of the seven actors who have appeared in the show since the pilot, only Donald Faison and John C. McGinley were set to retain their roles as regulars.

Zach Braff returned part-time and was absent for the majority of the season, while retaining first star billing for the six episodes he attended.

Sarah Chalke returned for four episodes as a guest star ; Although credited as a guest star, Ken Jenkins appeared in the majority of the season, appearing in nine of the thirteen episodes ; Neil Flynn appeared in the season premiere in a brief cameo ; and Judy Reyes was absent the entire season, making her the only former star not to return to the show.

Her character Carla is only mentioned occasionally and Turk is seen speaking with her by phone in the end of one episode.

The new main cast included Eliza Coupe returning to the recurring role of Denise " Jo " Mahoney from season eight, Dave Franco as Cole, a charming, confidently stupid and incredibly entitled medical student whose family donated the money to build the school, Kerry Bishé as Lucy, who shared the starring role with Braff in the beginning of the season and eventually became the show's new narrator, and Michael Mosley as Drew, a 30-year-old med student on his last attempt at school.