Isringhausen notched the milestone save with runners on second and third as the Mets beat the San Diego Padres 5-4 in 10 innings on Monday night. The save came after Scott Hairston drove in the go-ahead run with a fielder's choice in the top of the inning.
The Mets had a small champagne party in the clubhouse afterward.
"I'm just glad it's over with so we can move on, hopefully, maybe get 301 tomorrow. I'm happy I got it, but I've got another game tomorrow," said Isringhausen, a 38-year-old former Mets' phenom who is in his first season back after missing 1 1/2 years due to injuries.
Isringhausen said getting 300 saves was the reason he came back.
"Now it's time to move on for myself and keep playing baseball and hopefully get a few more saves before the end of the year," he said.
Starter R.A. Dickey said the night should be about Isringhausen.
"Unfortunately we haven't given him very many opportunities over the last week but I'm thankful that he got another one tonight. I'm just glad to be part of it in a small way."
Isringhausen allowed a walk and a single in the 10th before securing his seventh save in 11 chances this season.
"It puts him in the elite group of closers that have ever pitched in this game," manager Terry Collins said. "I'm sure he's been on pins and needles all week long. I'm just glad he got it out of the way. It's certainly deserving and I'm really happy for him."
Manny Acosta (1-0) got the win after pitching the ninth.
After letting the Padres tie the game in the eighth, the Mets opened the 10th with consecutive walks by Jason Pridie and Thole against rookie left-hander Josh Spence (0-2). They advanced on a sacrifice bunt by Ruben Tejada off Chad Qualls. Pridie scored when Hairston, a former Padres player, hit a hard grounder to shortstop Alberto Gonzalez with the infield drawn in. Gonzalez fielded the ball and fell backward. He had no play at first but the Padres threw out Thole at third.
Dickey, who had lost his previous three starts, took a no-decision. He was chased by Will Venable's two-run homer in the seventh that pulled the Padres to 4-3. The Mets scored as many runs for Dickey on Monday night as they had in his previous three starts.
Dickey allowed three runs on seven hits in 6 1/3 innings, struck out four and walked one.
San Diego starter Aaron Harang left in the sixth inning after a comebacker by Thole hit him on the right wrist or hand. Even so, Harang had thrown 93 pitches and reliever Erik Hamren was already warming up in the bullpen.
Harang went five-plus innings, allowing four runs and eight hits while striking out four and walking three.
Thole had a two-run homer and Duda a solo shot that gave the Mets a 3-0 lead off Harang in the second. Duda opened the inning with a shot deep into the seats in right field, his fifth. After Pridie walked with one out, Thole reached the home run porch down the right field line, his fourth.
"I just made some poorly located pitches and they took full advantage of it," Harang said. "I had to battle out there. The last couple of starts I've been making some bad pitches in situations that have come back to hurt me."
Thole added an RBI single in the fourth to make it 4-1, and singled again in the sixth.
It was New York's third win at Petco Park in 13 games. ... Jonathon Niese (11-9, 4.03 ERA) starts for the Mets on Tuesday night. ... Niese lost 3-2 against San Diego at Citi Field on Thursday. ... The Padres counter with Cory Luebke (4-6, 3.09) in a matchup of lefties. ... Luebke has gone with 3-4 with a 2.98 ERA with 56 strikeouts against 11 walks in nine starts since joining the rotation. ... The Padres agreed to terms with RHP Joe Ross, the second of their two first-round draft picks, as well as RHP Michael Kelly and C Austin Hedges. They are three of the team's six top picks and agreed just before Monday night's deadline. ... The Mets signed their first-round pick, OF Brandon Nimmo of Cheyenne (Wyo.) East High.