Looper was inconsistent with the Marlins, working his way into the closer role. However, he had a penchant for blowing easy saves. Toward the end of the 2003 season, as the Marlins were in a pennant race that culminated in a World Series win, Looper faltered and was replaced as closer by Ugueth Urbina. Looper appeared in relief in the fourth game of the World Series, which went 11 innings. His performance gained him a win, as the Marlins won the game in the bottom of the 11th.
In January 2004, Looper signed with the New York Mets as a free agent and had his best season to date going 2-5 with 29 saves and a 2.70 ERA. However, Looper had many crucial blown saves during the 2005 season, including blown saves on Opening Day, in a game that would have clinched a Met sweep at Yankee Stadium and as part of an eight-run collapse by the Mets pen against the Nationals. These performances still fresh in fans' minds, he was greeted with loud boos and "Looper sucks!" chants upon his returns to Shea with the Cardinals, most prominently during the 2006 NLCS.
In September 2005, Looper underwent shoulder surgery to repair a blown AC joint. This, in addition to the emergence of Aaron Heilman and acquisition by the Mets of other relief pitchers, kept the Mets from picking up his $5 million option for 2006. On December 15, 2005, he signed a three-year, $13.5M contract with the Cardinals to set up star closer and former Met Jason Isringhausen.
Beginning in the 2007 season Looper became a starting pitcher for the first time in his major league career. Before the season began, Looper stated that his goal was to reach 200 innings pitched in the season. In his first season as a starter, Looper reached career highs in wins (12), innings pitched (175), and strikeouts (84) in 30 starts (31 total appearances).
On October 30, 2008, Looper filed for free agency.
After the 2009 season the Brewers did not pick up the option on Looper for 2010, making him a free agent.
After not pitching in the 2010 season, Looper was a non-roster invitee of the Chicago Cubs to spring training as a candidate to be either a starter or reliever on the team. Looper had stated that the Cubs were the only team he would attempt a comeback with. However, on March 25, Looper was informed he would not make the opening day roster, and he retired.
Looper is married with and resides in Frankfort, Illinois. He and his wife, Shannon, adopted a daughter named Gracyn from China in 2009. Their biological children are Toryn and Landen. His cousin, Aaron, is a former major league relief pitcher.