With the retirement of David Ortiz and the offseason addition of first baseman Mitch Moreland, Ramírez took on the role of designated hitter for the Red Sox. He had his lowest major league batting average as part of a .242/.320/.429 slash line, with 23 home runs, 62 RBI, and just one stolen base (the lowest total of his career) while playing only 18 games in the field, all at first base). In the postseason, Ramírez batted 8-for-14 (.571) in the 2017 ALDS as the Red Sox lost to the eventual World Series champions, the Houston Astros.