On January 4, 2002, Gardenhire was named manager of the Twins, replacing Tom Kelly, who had won two World Series titles with the Twins. In contrast to Kelly's relatively calm, Bud Grant-like coaching style, Gardenhire was a very active and aggressive manager, frequently exiting the dugout to argue with umpired, leading some to joke that "Gardy" got ejected more times in a season than Kelly did in his entire career. In his 13 seasons managing the Twins, Gardenhire was ejected 73 times. An early 2006 television commercial for the Twins pokes fun at this, showing Gardenhire arguing with an office worker planning to go home after work rather than go to the Twins game.
In thirteen seasons as the Twins' manager, Gardenhire's team had a losing record five times (2007, 2011, 2012, 2013 and 2014), and won the division six times (the Twins lost a one-game playoff to the Chicago White Sox to determine the division champion at the end of the 2008 season). Despite all of the team's regular season success under Gardenhire, the Twins advanced to the American League Championship Series only once – his first season, in 2002 – and did not reach the World Series. In Gardenhire's tenure as the manager of the Twins, the team posted a playoff record of 6 wins and 21 losses. He is the only manager in major league history to take a team to the playoffs at least six times and never make it to the World Series, and only one of four with at least four playoff appearances to never appear in it.