BOSTON - Grady Sizemore delivered a game-winning single with nobody out in the 12th inning, giving the Boston Red Sox a 4-3 victory over the Cincinnati Reds in the opener of a two-game inter-league series on Tuesday night.

Designated hitter David Ortiz, playing in his 2,000th major league game, opened the 12th win a single off loser Logan Ondrusek (0-2) and moved up on first baseman Mike Napoli's single. Ortiz seemed to be looking into the dugout for a runner, but it didn't matter as Sizemore then came through with his third hit of the night, a long drive off the wall in left-center, scoring Ortiz from second.

It was the fourth walk-off hit of the comebacking Sizemore's career, but the first since Aug. 11, 2006.

Left-hander Craig Breslow (1-0) pitched the top of the 12th, striking out two and getting the win.

Red Sox closer Koji Uehara pitched out of trouble in the ninth, when rookie catcher Tucker Barnhart hit one almost 380 feet that was run down by right fielder Shane Victorino -- a ball that's a home run in warmer weather or in most ballparks.

Left-hander Andrew Miller struck out four in two scoreless innings before Breslow came on.

The Reds, making their second visit to Fenway Park since winning the classic 1975 World Series, tied the game with two runs off right-hander Junichi Tazawa in the eighth inning. A walk, a double by second baseman Brandon Phillips, an RBI single by third baseman Todd Frazier and a sacrifice fly by left fielder Ryan Ludwick tied the game.

Napoli drove in two runs for the Red Sox, while second baseman Dustin Pedroia had three hits, including the 299th and 300th doubles of his career.

Boston left-hander Felix Doubront, who hasn't won since his first start, left with the lead after working 5 1/3 innings. But he had a lead blown for him for the second time in his six-start drought.

Reds starter Homer Bailey pitched six innings, allowing three runs.

Right-hander Burke Badenhop relieved Doubront with two on and one out in the sixth and his first pitch was turned into a 4-6-3 double play started by Pedroia. Badenhop worked a perfect seventh before Tazawa came on and blew the setup.

The Red Sox (16-17) will again try to get back to the .500 mark in the series finale on Wednesday night. Since losing its fifth game of the season to fall to 2-3, Boston has had five chances to reach .500 and failed all five times.

The Reds, who are battling injuries, fell to 15-17.

The Red Sox reached Bailey for a run in the first inning, when they were helped by Cincinnati shortstop Zack Cozart failing to properly touch second base on what should have been a double play. Napoli, returning after missing a start to rest his injured left ring finger, drove in the run on a check-swing groundout.

The Reds got the run right back in the second inning but could have had more. A walk and a double led to an RBI single by center fielder Skip Schumacher, his first RBI in just his third game of the season. With first and third and nobody out, the Reds failed to take the lead.

The home team moved in front in the third when Napoli walked with the bases loaded and Sizemore singled home a run. Boston had the bases loaded with one out but couldn't add to its advantage.

The Red Sox wasted a leadoff double by Ortiz and an ensuing walk to Napoli that started the fifth. Ludwick made a nice catch of a Sizemore drive at the scoreboard.

NOTES: Reds RF Jay Bruce, expected to miss as much as a month after Monday's arthroscopic right knee surgery, was placed on the 15-day disabled list. OF Roger Bernadina, recently outrighted to the minors, had his contract purchased from Triple-A Louisville. ... Reds CF Billy Hamilton's left hand was still too swollen to swing a bat, and the speedster missed his fourth consecutive start. ... Red Sox 2B Dustin Pedroia was praised by Mariano Rivera in Rivera's memoir, "The Closer," Rivera saying he would take Pedroia over former Yankees 2B Robinson Cano. "Not surprising. The ultimate compliment," Red Sox manager John Farrell said. ... Boston RHP Jake Peavy, 6-0 with a 2.14 ERA in 10 career starts against Cincinnati, pitches against Reds RHP Mike Leake on Wednesday night. ... Red Sox DH David Ortiz played in his 2,000th major league game Tuesday marked the 99th anniversary of Babe Ruth's first big-league home run, hit while pitching for the Red Sox.