Santiago is 10-5 with a 4.37 ERA this season with 111 strikeouts in 125 2/3 innings, but he leads the American League in walks (59) and homers allowed (22). He went five innings against the Indians, allowing four runs on five hits, with all four of those runs coming on two swings of the bat from Jason Kipnis and Carlos Santana.
"I made two bad pitches all-around," Santiago said. "They were two cutters that stayed in the middle. That's it."
Santiago gave up his first run in a Twins uniform in a hurry, surrendering a solo blast to Kipnis in the first on a 1-0 cutter after an 11-pitch at-bat against leadoff batter Rajai Davis. He also walked Mike Napoli with two outs and Napoli promptly stole second, but Santiago was able to get out of the jam by getting Santana to fly out to center.
"That's always tough," Twins manager Paul Molitor said of the long at-bat before Kipnis' homer. "He got him out, but then he gave up the homer to Kipnis. But there were some good things there. I thought when he needed a little extra velocity, it went up a couple times. He was a little erratic with the command of a couple of his pitches, but he hung in there."
Santiago, though, wasn't as fortunate in the third, when Francisco Lindor singled with two outs before Napoli drew a 10-pitch walk. Just two pitches later, Santana deposited an 0-1 cutter into the left-field stands for a three-run homer and the Twins never recovered.
"It was just a bad pitch, and usually in that situation, I make a better pitch," said Santiago, who had a 1.78 ERA over his previous six starts and hadn't lost a game since June 10. "It kind of took away the tone of the game of us right there."
Santiago's pitch count prevented him from going deep into the game, as he needed 99 pitches to get through five innings. It's been an issue for him this year, as he's averaging fewer than six innings per start.
"His pitches got up there rather quickly," Molitor said. "We just couldn't muster enough to get back into the game."
Rhett Bollinger has covered the Twins for MLB.com since 2011. Read his blog, Bollinger Beat, follow him on Twitter @RhettBollinger and listen to his podcast. This story was not subject to the approval of Major League Baseball or its clubs.