Finally healthy in 2008, Romero struggled with control problems with a career high 55 walks for the Double-A New Hampshire Fisher Cats.

He received a late year call up to Triple-A Syracuse and earned Player of the Week honors as a member of the Chiefs on September 1.

[4] On March 30, 2009, Blue Jays manager Cito Gaston announced that Romero had earned one of the two open rotation spots for the 2009 MLB season.

[5][6] On April 9, Romero made his Major League debut against Detroit, opposite Tigers rookie pitcher Rick Porcello.

He had a 2–0 record and a 1.71 ERA in his first three starts, but was placed on the 15-day disabled list on April 20 with a strained right oblique muscle after a violent sneeze.

[9] The Jays, surprising many observers by holding first place for the month of April despite many injuries to their key pitchers, hoped he would be ready to return to their lineup by mid-May.

[10] Romero was called up from Triple A Las Vegas 51's along with Casey Janssen, after a successful rehab assignment in the minor leagues to evaluate his progress.

Others included Chicago White Sox infielders Gordon Beckham and Jayson Nix, as well as Detroit Tigers starting pitcher Rick Porcello.

On April 13, 2010, Romero set a new career high with 12 strikeouts while allowing only two runs on one hit over eight innings in a 4–2 victory over the Chicago White Sox.

On June 26, 2011, Romero got his first major league hit, a two RBI single to right field, while pitching a complete-game shutout against the St. Louis Cardinals to complete the sweep.

[citation needed] Romero set personal highs for a single season with his second shutout and fourth complete game on August 18 against the Oakland Athletics.

[21] On April 11, 2012, in the fourth inning of a game against the Boston Red Sox, Romero recorded his 500th career strikeout against outfielder Darnell McDonald.

No physical reason appeared to exist for Romero's sudden turn in performance, and the Jays kept him in the rotation for the entire season.

Romero spent time in an extended spring training camp, and was recalled from Dunedin on May 3, 2013, after having pitched only one official game in minor league play.

[30] His contract was selected by the Blue Jays on September 3 after the Bisons season ended, and the major league rosters expanded.

In early August, Romero was placed on the Toros reserve list, rendering him inactive as a player, while still keeping his contractual rights tied to the team.