Colón made his Major League Baseball debut against the Anaheim Angels on April 4, 1997, receiving a no decision. In his first MLB season, Colón went 4–7 with a 5.65 ERA. The following year, he set the modern-day but unofficial MLB record for throwing the most pitches (20) in a single at bat on June 26, 1998 against Ricky Gutiérrez, who eventually struck out. That record would not be broken until 2018. Later that season, Colón won his only start of the 1998 American League Championship Series, pitching a four-hit, one-run complete game. In his 1999 season, Colón finished 18–5, pitching over 200 innings with 161 strikeouts and a 3.95 ERA.