Nathan started the season with 13 consecutive saves but blew his first save of the season on May 27 by giving up a three-run inside-the-park home run on a misplayed fly ball by teammate Delmon Young; however, Nathan got two outs to end the 9th inning and the Twins went on to win the game. By converting 27 of 29 save opportunities prior to the All-Star break, Nathan was selected as a reserve player for the American League in the 2008 Major League Baseball All-Star Game. Nathan finished the year with 39 saves and a career best 1.33 ERA. He also had a career high six blown saves and surrendered his first career walk-off home run to Victor Martinez on September 16. Nathan ranked seventh in the majors in saves and had the lowest ERA of the top 30 save leaders in 2008.