He played in Major League Baseball (MLB) for the Houston Astros from 2005 to 2012, the Pittsburgh Pirates from 2012 to 2014 and the Texas Rangers in 2015.

Rodríguez performed decently in the game 1 of the series, relieving Roger Clemens in the third inning with the score tied at 3.

Rodriguez surrendered one more run in the bottom of the fourth inning, earning the loss as the White Sox went on to win, 5–3.

Brandon Backe was activated from the 60-day disabled list to take his place on the major-league roster and the Astros rotation.

Rodriguez had his first full healthy season in the majors, as he started and played in 31 games, finishing with a 4.58 ERA and a 9–13 record, along with 158 strikeouts in 182 innings.

However, his performance was a big improvement statistically, finishing with a 3.54 ERA and a 9–7 record, along with 131 strikeouts and a perfect fielding percentage.

[5] Rodríguez had a career year in 2009, after being moved up into the second spot in the Astros' rotation behind ace Roy Oswalt.

[6] Rodríguez regressed from his 2009 campaign in the first half of 2010, going 6–11 with a 4.97 ERA with only 77 strikeouts in 101+1⁄3 innings pitched prior to the All-Star break.

[7][8] To begin the 2012 season, Rodríguez was the last Astro (player or coach) remaining from the 2005 squad that went to the World Series.

On July 24, 2012, the Pittsburgh Pirates traded Rudy Owens, Robbie Grossman and Colton Cain to the Houston Astros for Rodríguez and cash.

[14] However, he failed his physical examination performed by Phillies' doctors, and subsequently signed a minor league contract with the Atlanta Braves.