Trying to protect a one-run lead in the ninth inning, he fell behind Jose Reyes 3-0, then walked him with the count full.
"Committed the No. 1 sin," Isringhausen said. "That's when the adrenaline starts kicking in again."
Reyes advanced to second on a bunt before Isringhausen got out of trouble Saturday, preserving St. Louis' 7-6 win over the New York Mets.
"You're not going to have a 1-0 game all the time," said Mulder, whose ERA rose from 2.70 to 3.44.
Kaz Matsui chased Mulder with a tying three-run triple in a four-run sixth inning, but the Mets failed to hold a 6-5 lead in the eighth, when pinch-hitter Larry Walker had a go-ahead sacrifice fly off Roberto Hernandez (2-1).
Mulder had won five straight starts, allowing just five earned runs. But given a 5-2 lead, he gave up singles to Mike Cameron and David Wright in the sixth, and loaded the bases with a 10-pitch walk to Ramon Castro.
Matsui poked his opposite-field triple into the right-field corner.
"It's inexcusable," Mulder said. "I've got to do a better job."
Matsui had been in a 2-for-27 slide that dropped his average to .223. With his defense also shaky, many fans at Shea Stadium booed him.
"There's no booing in Japan," he said through a translator.
Mulder allowed six runs and 10 hits in five-plus innings. Martinez gave up five runs -- four earned -- and five hits in six innings.
"I didn't have a good changeup today," Martinez said. "It kept flying around. I was leaving it up. Sometimes it's lack of work in the bullpen. I didn't throw this time between starts."
His next scheduled start is Friday in the opener of the first series of the season between the Mets and Yankees.
"Why is that game any more important than the game today?" Martinez said. "I never had issues with the Yankees. They beat me. I beat them."
John Mabry grounded out with the infield in and Mark Grudzielanek, who tied a career high with four RBI, loaded the bases with a walk. Walker batted for So Taguchi and lofted a fly to left that drove in Pujols.
New York almost came back in the ninth. After the walk to Reyes and Miguel Cairo's sacrifice, Isringhausen retired Carlos Beltran on a flyout. The right-hander intentionally walked Cliff Floyd, who is 4-for-12 against him, then struck out Cameron for his eighth save in eight chances.
Isringhausen had been sidelined by a strained abdominal muscle.
"That's not what you want to do, one-run lead, top of the lineup, all kind of danger," Cardinals manager Tony La Russa said. "That's one thing about Izzy, he's never afraid. You give him anything, and he's absolutely fearless."
Julian Tavarez (1-1) pitched 1 2/3 scoreless innings for the win.
Mets manager Willie Randolph thought the game turned after the Mets went ahead in the sixth. With runners at the corners and none out, Reyes was caught stealing. Thompson then retired Cairo and Beltran.
"We should have scored more runs out of that," Randolph said.
Reyes took off early on his own, and Thompson had plenty of time to step off the rubber and throw him out at second.
"What I did there was wrong," Reyes said. "I just put my head down and ran for the next base."
Martinez's previous appearance against the Cardinals was in Game 3 of last year's World Series, when he allowed three hits in seven shutout innings, retiring his last 14 batters in Boston's 3-0 victory. He got his first four in this one before walking Mabry and giving up a long two-run homer to Grudzielanek.
Grudzielanek made it 3-0 in the fourth with an RBI single. New York pulled within a run in the bottom half when Wright hit an RBI double and scored on Castro's single. Nunez homered leading off the sixth, and Grudzielanek hit a sacrifice fly after Cairo let a grounder to first carom off his glove into foul territory for an error.
Grudzielanek, 0-for-2 against Martinez coming in, sounded surprised by his success against him.
"I played with him for a few years, so I kind of knew what he did back then," he said. "But he's a different pitcher now."
- Grudzielanek had four RBI for the fifth time, the first since June 1, 2001, for Los Angeles at Houston.
- Martinez has allowed four homers in his last two starts after giving up one in his first six.
- Scott Seabol of the Cardinals pinch-hit in the seventh and singled for his first major league hit.