In , Mitre started out the season on the Opening Day roster, filling in for the injured Mark Prior. He was sent down to the Triple-A Iowa Cubs after Prior came back from injury. On August 13, 2004, Mitre pitched a complete game shutout against the Albuquerque Isotopes. Mitre gave up only a double and a walk, both coming in the first inning of the game. After this, Mitre sat down 23 straight batters, striking out 9 batters in the game. He became the Pacific Coast League's Player of the Week. He finished the Iowa Cubs 2004 season (after going back and forth to Chicago) with a 6–4 record, and a 2.97 ERA.