Worrell's greatest success came in 2003 when he replaced the injured Robb Nen as the closer for San Francisco. After the season Worrell signed with the Philadelphia Phillies, where he returned to his previous role as a set-up pitcher, often pitching the eighth inning before Phillies closer Billy Wagner entered the game.
On December 1, 2005, Worrell's return to the San Francisco Giants was agreed, with a two-year contract valued at $4 million.
On January 10, 2007, he announced his retirement due to a persistent nerve Problem in his neck. Worrell stated that his major league career is not completely over as he wanted to get into coaching. He is currently the rehab pitching coach for the Peoria Padres.