The left-handed starter pitched three scoreless innings in his season debut before a tough fourth inning cost him the game as Toronto fell to the Seattle Mariners 4-0.
Romero (0-1) struck out four but gave up three earned runs and three walks in the fourth. He was hit in the forearm by a hit from Jesus Montero, but still made the play at home to get a forced out. A popfly by Brendan Ryan ended the inning and Romero was pulled with a knot forming from the shot to his pitching arm.
It was a disappointing outcome for the 28-year-old who started the season in the minor leagues after struggling through spring training.
"(The start) felt like the guy I'd been working on this past month in Florida. Felt good, had some good stuff, had a lot of live movement on the fastballs," said Romero. "That fourth inning just kind of got away from me a little bit and unfortunately I got hit by that ball and it got me in a pretty good spot."
Blue Jays (10-20) manager John Gibbons said that X-rays came back negative on Romero's forearm.
"He ran into trouble and he survived that inning," said Gibbons. "He got a couple big outs there late and he got that come-backer, it hit him, but he made a nice play at the plate.
"He ought to feel real good about that game."
Romero has 126 career starts with Toronto, earning a career 51-44 record. He was called up from single-A Dunedin on Thursday after Josh Johnson was placed on the 15-day disabled list with an inflamed right tricep.
Romero has lost eight straight decisions over nine starts at Rogers Centre, stretching back to last season.
Felix Hernandez (4-2) pitched an eight-inning shutout with seven strikeouts for Seattle (14-17), while third baseman Kyle Seager led the Mariners with three hits, including a two-run homer.
"(Hernandez is) special. He goes about his business," said Seager. "You give him a couple of runs and you know he's going to take care of the rest."
Jason Bay of Trail, B.C., also had a home run for Seattle.
After three scoreless innings, Romero began to struggle with ball control.
He walked Victoria's Michael Saunders to start the fourth inning, then gave up a home run to Seager. He hit Kendry Morales with a pitch, who advanced to second on a wild pitch.
At this point, Romero seemed bothered by his throwing hand and coaches and a trainer came out to the mound. After a brief meeting, Romero stayed in the game.
"He's got a callus and he kept looking at that, which is why we went out there the first time, but that's no big deal," said Gibbons.
Romero insisted that the callus didn't affect his pitching and that he would've continued the game if he hadn't been struck by the ball.
"(The callus) is something that I've had and we've just been taking care of it," said Romero. "I think I just lost control of where the fastball was going. Almost seemed like I was spiking it.
"One of the things we've been working on is pitching down in the zone and I think that at times I was a little bit too down."
Romero's troubles returned after striking our Michael Morse as he walked Bay and Justin Smoak to load the bases.
A single by Dustin Ackley cashed in Morales and the come-backer by Montero forced an out at home. Brendan Ryan then popped out to second to end the fourth but the damage was done: Romero had faced all nine Mariners hitters in a single inning and Toronto trailed 3-0.
"I thought he was great, I really did," said Gibbons of Romero. "He ran into some trouble there that last inning with some walks and hitting the batter, but overall I thought he should feel good about that outing, something to build off of.
"At the beginning of the game I thought he was dynamite. I know he's a little disappointed in that, but I think it's a good starting point.
Blue Jays reliever Aaron Loup got through the fifth without any trouble, but then gave up a solo home run to Bay in the sixth after Morse grounded out. Smoak and Ackley hit back-to-back singles to put runners at first and second.
Montero hit a ball to deep right field, but Jose Bautista caught the ball at the wall and fired it in to second base to keep either runner from advancing. Ryan then hit into a forced out at second to end the inning.
Reliever Esmil Rogers had a three up, three down seventh inning for Toronto, but Hernandez stayed dominant. Bautista singled to left field, but Edwin Encarnacion hit into a double play. Hernandez then struck out J.P. Arencibia to retire the side and maintain Seattle's 4-0 lead.
The Blue Jays threatened again in the eighth inning as first baseman Adam Lind hit a double to deep centre-right field. He advanced to third when Colby Rasmus singled into right field.
Toronto was neutralized when Maicer Izturis hit the ball directly to Ryan, who threw Rasmus out at first. Munenori Kawasaki then ground out to short to end the Blue Jays' inning.
"I wish I could've gotten deeper into the game, especially the way the bullpen's been worked these past few games," said Romero. "Just looking forward to working for my next one."
Tom Wilhelmsen came in to pitch the Mariners' ninth inning, inducing a ground out and a pop fly before walking Bautista. He then ended the game by striking out Encarnacion.
Notes: Toronto Marlies forward Mike Zigomanis threw out the opening pitching. The Marlies have time off while they wait for their second-round opponent in the American Hockey League's playoffs. ... Announced attendance was 23,779.