On January 19, 2011, Pavano agreed to a 2-year contract with the Twins. He was paid $8 million in 2011 and $8.5 million in 2012, along with up to $500,000 in incentives.
On May 1, 2011, after performing poorly against the Kansas City Royals, Pavano took a bat to a trashcan in the Minnesota Twins dugout after being removed in the sixth inning of a 10-3 loss. Pavano responded by saying "That's as frustrated as I can get. It actually felt pretty good. I just kept whaling away with it. The (bat) wouldn't break. I couldn't break a bat in the dugout and I couldn't break any out there (on the mound). It was embarrassing." Pavano's stats as of his May 8 start were 2–4 and an ERA of 6.64, the highest of any Twins pitcher at this point in the season. However, on May 13, 2011, Pavano threw 5 1/3 scoreless innings against the Blue Jays but got the no decision in the Twins 2–0 loss. His pitching continued to improve through late May and early June. Pavano recorded his 100th win in a complete game 2-run performance on June 3 against Kansas City, and he pitched another complete game win 12 days later against the White Sox. Pavano continued the season with mixed success. He finished with a 9–13 record and a 4.30 ERA, closing out the Twins' season with a shutout of Kansas City Royals. Of the five starting pitchers for the Twins in 2011, Pavano was the only one who remained in the rotation for the entire season. Francisco Liriano, Brian Duensing, Nick Blackburn, and Scott Baker all missed starts due to injuries.