After bowing out of the 2015 playoffs, partly due to a bullpen meltdown in the ALDS, the Astros went into the offseason searching for a flame-throwing reliever. On December 12, 2015, Giles was acquired from the Phillies to fill that void. Houston included top pitching prospects Mark Appel and Vincent Velasquez in a package to add the 25-year old right­hander. The owner of a 1.56 ERA and a strikeout rate of 11.7 per nine innings in 113 relief appearances with Philadelphia, "100 Miles Giles" had his own meltdowns both on and off the field, falling out of favor with Houston's management. In the 2017 World Series, he was called on twice and wasn't asked to close in a tight Game 7.

At the 2018 trade deadline, Giles was dealt to Toronto for another closer with a questionable reputation, Roberto Osuna. Through 2019, the native of New Mexico owns a 14-18 record with a 2.67 ERA and 114 saves.