During spring training in 2005, Nathan signed a two-year deal that includes a club option for 2008. He picked up from where he left off in 2004, allowing no earned runs in 15 appearances from April 5 to May 10. He also had streaks of 13 and 12 consecutive save opportunities converted between April and July. As a result, Nathan was named the American League Player of the Week for the week of June 27. Nathan earned another All-Star appearance in 2005 for his pitching in the first half of the season. Although his record was 1–3 with a 3.57 ERA in 37 appearances, he had struck out 43 batters in 35 innings pitched, and lead the AL with 23 saves in 25 opportunities. Nathan pitched in the 2005 MLB All-Star Game alongside fellow pitcher Johan Santana. Pitching the eighth inning of the game, he got Morgan Ensberg to pop out for the first out, then gave out a double to Moisés Alou. Felipe López singled, and Nathan was able to get Miguel Cabrera and Luis Castillo out, but not before Alou scored. Nathan had a brilliant second half as he went 6–1 with 18 saves in 20 chances, and posted an ERA of 1.76. He finished the season with a 7–4 record, a 2.70 ERA, 43 saves in 48 opportunities, and 94 strikeouts. Nathan also became the third pitcher in club history to post consecutive 40 save seasons. The Twins however missed the playoffs.