The Devil Rays converted him to a relief pitcher, and he made his major league debut with them on June 21, 2001. He finished with a 3.33 ERA. Colomé was one of the only pitchers to throw over 100 mph, but he had bad control. The next season, he posted an 8.27 ERA (the highest of his career). He returned to his old form in 2004, in 2003 he struck out a career high 69 batters.
On August 26, 2005, Colomé was involved in a serious car accident in the Dominican Republic. Two months later, he was released by the Devil Rays.
Colomé signed a minor league contract with the New York Yankees in 2006. At the end of the season, spent entirely in the minors, he opted for free agency.
Colomé then signed with the Washington Nationals. He came north with the Nationals following the spring season and started off pitching well. By Memorial Day he was 4–0, and was fifth in the league with 26 appearances, posting a 2.20 ERA and prompting MLB writer Bill Ladson to write, "Jesús Colomé is the Nationals' best reliever, and one could argue that he should be considered for the All-Star Game."[1] Ladson credited Colome's resurgence in his reliance on pitches other than his once dominating fastball.
On December 10, 2008, he was released by the Nationals.[2] He was re-signed by the Nationals to a minor league contract on January 15, 2009. He competed for a spot on the Nationals' roster in spring training, but was sent to the minor leagues on April 4, 2009.[3]
In July 2009, the Nationals designated him for assignment and he was picked up by the Milwaukee Brewers and signed to a minor league contract. On September 6, he was released by the Brewers.
He was signed to a minor league contract by the Los Angeles Dodgers on June 23, 2010, and assigned to the AAA Albuquerque Isotopes. He only appeared in 3 games for the Isotopes before he was released.
