Pujols hit a game-winning single in the ninth inning after Isringhausen allowed a tying home run to Jose Hernandez in the top half, giving the Cardinals a 4-3 victory over the Pittsburgh Pirates on Wednesday and a three-game sweep.
Pujols, who leads the majors with 29 RBI, has the game-winning RBI in four of the Cardinals' last five victories.
"Izzy, I know he wanted to get that save right there, and he made a mistake," Pujols said. "But we came out with a win, and everybody will forget about what happened."
St. Louis led 3-2 with two outs in the ninth when Hernandez hit his first homer of the season. Isringhausen (1-2) has allowed three homers in eight innings this year, two resulting in losses, and has a 6.75 ERA.
"Just one bad pitch I wish I could get back, but I can't," Isringhausen said. "It's just frustrating more than anything, but we'll be back out there."
The Hernandez homer denied Mark Mulder his 100th career victory. Then, in the bottom half, David Eckstein and Hector Luna hit consecutive singles off Roberto Hernandez (0-1), and Pujols lined a 2-2 pitch down the third-base line.
Pujols was down 0-2 earlier in the count.
"I know if I get two strikes, I can still take the same approach and get a base hit," Pujols said. "I'm really comfortable with two strikes, it doesn't bother me at all."
Hernandez thought he had Pujols struck out on an 0-2 pitch.
"If he doesn't swing 0-2, it's not a strike," Hernandez said. "He's such a great hitter and such a great competitor, anyway, and now you consider him like Barry Bonds, when he was going good."
Pujols didn't want to talk about the location of the 0-2 pitch.
"If I was an umpire I would tell you so," Pujols said. "Maybe the pitch was good, but he didn't call it, so I don't have anything to say about that."
Luna, who went 2-for-5 and raised his average to .432, had his fourth straight multihit game for the Cardinals, who have won six of seven overall. They're 29-10 against the Pirates since 2004 and swept them for the first time since May 23-25 last year.
They won the finale without Scott Rolen, sidelined for the second straight day by bronchitis, and Jim Edmonds, who got a day off against a left-handed pitcher.
Juan Encarnacion, batting cleanup for the first time this season, hit a sacrifice fly in the fifth off Zach Duke to break a 2-2 tie. Encarnacion has five RBIs the last two games after totaling one in the first 19.
Craig Wilson hit a two-run homer in the fourth for the Pirates, who have a season-worst seven-game losing streak. They've been outscored 34-12 during the slump, have lost 12 of 13 on the road and are an NL-worst 5-18.
"We've had a few like this," manager Jim Tracy said. "The record may suggest differently, but when you look at the games we've played, we've had our fair share of games like this."
Mulder allowed two runs and five hits in 7 2/3 innings.
Scott Spiezio, starting for the second straight game, was 2-for-4 with a run-scoring single in the first. Miles, playing second base for the first time since a two-error game on Sunday, had an RBI single in the second for a 2-0 lead.
Pittsburgh had two runners on before Wilson grounded into an inning-ending double play in the first. He didn't miss his next chance, hitting his seventh homer to tie it in the fourth.
Duke gave up three runs, eight hits and five walks -- three intentional -- in six innings. Last season, Duke stopped a pair of five-game losing streaks, plus a three-game skid.
- Jack Wilson was 0-for-2 with a walk and a sacrifice, ending an eight-game hitting streak.
- Paid attendance of 38,728 gave the Cardinals their 12th sellout in 12 games at the new Busch Stadium.
- The Cardinals have won six of seven series this season -- the exception was a Cubs' sweep in early April. This is their second sweep of the season; they also took three straight at Philadelphia to open the season.