Sambito made the Red Sox roster out of spring training in . He would go on to post a 2–0 record with 12 saves that season, and helped the Red Sox reach the World Series. Arguably his most memorable save as a Red Sox came on June 17, 1986. Holding onto a 1 run lead, Sambito retired Don Mattingly and Dave Winfield with the bases loaded to close out the game. He retired in 1987 after posting a 2–6 record with 6.93 ERA. In an eleven-season career, Sambito posted a 37–38 record with a 3.03 ERA and 84 saves in 461 games.