Following the trades of Billy Wagner in the 2003 off-season and Octavio Dotel in the summer of , the Astros moved Lidge from setup man to closer. He set a new National League record for strikeouts by a reliever with 157, passing Goose Gossage's total of 151 set in 1977. The mark is third all-time for relievers, behind Dick Radatz's 181 in , and Mark Eichhorn's 166 in .
Later in 2005, Lidge finished the season with a 2.29 ERA and a career-high 42 saves. That year, Lidge ranked third in the National League in saves and became the second Houston Astros pitcher ever to record at least 40 saves in one season alongside Billy Wagner.
During the 2005 NLCS, Lidge gave up a 3-run home run to Albert Pujols in Game 5 in Houston which forced a Game 6 back in St. Louis, which the Astros would win to clinch their first World Series berth in franchise history. In Game 2 of the 2005 World Series, Lidge gave up a walk off home run to Scott Podsednik. It was only Podsednik's second home run the entire year and it put the White Sox up 2-0 in the series; they proceeded to sweep the Astros to win the championship.
However, Lidge was demoted from the closer's role on April 9, 2007. Lidge would later regain his role in mid-June as the closer after going 10+ scoreless innings and posting a 2.45 era. On July 17, 2007, Lidge pitched a scoreless ninth inning against the Washington Nationals, striking out two and walking one, to earn his first save of the 2007 season. Lidge finished the season 5–3 with 19 saves in 27 chances for the Astros. On November 7, 2007, Lidge was acquired by the Philadelphia Phillies along with infielder Eric Bruntlett in exchange for outfielder Michael Bourn, pitcher Geoff Geary, and minor leaguer Mike Costanzo.
During the early 2008 season, Lidge showed signs that he regained the dominant form he displayed in his earlier career. In the opening two months of the season, he converted 12 save opportunities and allowed just two earned runs. In May, Lidge returned to Minute Maid Park, where he was greeted by a mixed reaction from Astros fans, but he recorded his 12th save of the season against his former team. He opened the month of June, usually the start of the summer's heavy-hitting season, with three saves earned in three straight games versus the Florida Marlins and the Cincinnati Reds.
In July 2008, Lidge signed a 3-year contract extension with the Phillies. This was partially a reward for his performance so far during the season, but also served the purpose of keeping him off the open market in the offseason; it saved the team from having to compete for his services. Lidge also set new Phillies records by converting his first 19 save opportunities and 35 straight saves.
Lidge was named to the roster of the 2008 Major League Baseball All-Star Game. He was announced before the game as the closer. After warming up six separate times, he ended up the final pitcher available in the game, and pitched in the 15th inning. He allowed a game-winning sacrifice fly in the bottom half of the inning, as the American League won the game, 4–3.
On September 27, 2008, Brad Lidge became the first closer in Philadelphia Phillies history to be perfect in regular season saves, converting 41 in as many opportunities, as he secured the National League East division title for the Phillies. He was awarded the 2008 MLB Comeback Player of the Year Award for his efforts. He is the first closer since Eric Gagné in 2003 to have a perfect conversion rate and 30+ saves. Brad Lidge finished the 2008 season with 41 out of 41 Save opportunities,a 1.95 ERA and 92 Strikeouts in 62 games.
The following is a breakdown of Lidge's regular season saves, blown saves, earned run average, and win-loss record throughout his career :
Note: After recording three saves in the beginning of the 2005 postseason, Lidge the went 0-3 with one blown save in his last five games that postseason.