On January 17, 1957, Sisler was re-signed by the Red Sox. The Red Sox expected Sisler to be a candidate for a pitching rotation slot. He impressed his coaching staff during early spring practices, manager Mike "Pinky" Higgins commented that Sisler "looks good; he's more mature and shows more confidence". When the regular season began, he was initially effective, winning three games against one defeat in his first four starts, including two complete game victories against the Yankees. At this point, he was 4–0 against the Yankees, earning him the moniker "Yankee Killer" from sportswriter Chester L. Smith of the "Pittsburgh Press". Although his ERA of 4.88 was considered high, it was due in large part to his loss against the Kansas City Athletics who scored six earned runs in just two innings. On July 4, he defeated the Yankees once again, making him 5–0 against them in his career, and 7–4 overall for the 1957 season, and had lowered his ERA to 4.02. That was his last victory of the season, however, which he followed with two consecutive losses, pitching a total of four innings; he did not appear in another game until September 2. He recorded a save against the Baltimore Orioles on September 7, but closed the season with two consecutive losses against the Yankees, though he pitched well in the second game, giving up just three hits and two earned runs in eight innings. His season totals include a 7–8 record, and a 4.72 ERA in 122⅓ inning pitched.