In 2012, Casilla took over as the Giants closer again after Wilson was injured and lost for the season in April. He converted 20 of his first 21 save opportunities but blew 5 of his next 9 save situations, posting a 7.71 ERA from June 23 through August 7. Bochy removed him from the role on August 7, replacing him with Sergio Romo and Javier López for the rest of the year. Casilla picked up his first career base hit, a bases-loaded, two-out RBI ground ball single between Diamondbacks first baseman Paul Goldschmidt and second baseman Aaron Hill, on September 14 in a 6–2 win. "I think we were all kind of shocked he made contact," Giants manager Bruce Bochy stated. "He found a good place." In 73 games, he had a 7–6 record, a 2.84 ERA, 55 strikeouts, 22 walks, and 55 hits allowed in innings pitched. Despite only serving as the closer for part of the year, Casilla tied with Kenley Jansen for 10th in the NL with 25 saves.
