Wyle’s big break came when he was given the pilot script for ER and was cast as medical student John Carter. He was the youngest member when he joined the cast. Wyle was the only major cast member of ER to have been with the show since its inception (1994) when he left after its eleventh season (2005). His performances on the show earned him Emmy Award nominations in each of its first five seasons. As part of an ensemble he was nominated several times for the Screen Actors Guild Award, he was recognized with three Golden Globe nominations as Best Supporting Actor in a Series, Miniseries or Motion Picture Made for Television and won the 2001 TV Guide Award for Supporting Actor in a Drama Series. Wyle left the series at the end of the eleventh season, although he returned in guest appearances for a four-episode arc during the twelfth season. He stated that he left because he wanted to spend more time with his family and friends and to make room for the upcoming generation. However, in 2009, Wyle returned to ER during its fifteenth and final season for five episodes, including the series finale. According to the Guinness World Records 2005 Special 50th Anniversary Edition, Wyle became the holder of a "Highest paid TV drama actor per episode" record during the 2003–2004 tenth season, earning approximately $400,000 per episode. While on ER, Wyle's estimated salary was $9 million a year. Wyle has also appeared in the most episodes of ER, 254, four more than Laura Innes.