J.D. Drew flies out to left field in the seventh inning, but his three-run home run in the third inning provided all the runs Boston would need to defeat Houston last night.

HOUSTON — Any fear that Daisuke Matsuzaka had not sufficiently recovered from shoulder fatigue during his three-week stay on the disabled list was erased last night as the Red Sox began their final interleague series of the season.

Five days after failing to get an out in the second inning in his first outing since returning from the DL, Matsuzaka tossed five shutout innings to send the Sox on to a 6-1 victory over the Houston Astros.

The Sox seemed poised to post back-to-back shutouts until Astros outfielder Reggie Abercrombie homered off Hideki Okajima in the eighth inning. It was the first run scored against the Boston bullpen in 12 innings, covering nine games. When Miguel Tejada followed with a hard single off the wall in left, Jonathan Papelbon was called upon to get the final four outs. He earned his 24th save of the season.

Earlier, Craig Hansen and Manny Delcarmen had each contributed a perfect inning out of the bullpen.

Matsuzaka, who improved to 9-1, allowed only two hits during his 87 pitches. He struggled some in the fifth when the Astros worked two walks around a single by catcher Humberto Quintero to load the bases with two outs.

But Matsuzaka got David Newhan to pop to shortstop Julio Lugo, leaving three Houston base runners stranded.

The win was the Sox’ third straight overall and fifth in their last six tries on the road. It improved the Sox’ interleague record to 11-5. With wins today and tomorrow, the team could eclipse the 12-6 record it had last season against National League opponents.

J.D. Drew, who will surely win American League Player of the Month honors for June, gave Matsuzaka — and the relievers who followed — all the necessary backing in the third with a three-run homer.

It was Drew’s 11th homer this month to go along with 26 RBI. Drew has more homers this month alone than he did in his first season with the Sox. He entered last night leading the majors in homers, total bases, extra-base hits and slugging percentage for June, while ranking second in RBI and runs scored.

Drew’s homer, off Houston starter Runelvys Hernandez, snapped a mini-slump for him. He had come into the game hitless in his last 13 at-bats and saw that grow when he struck out in the first.

The Sox padded the lead the seventh when Lugo led with a single, took second on a groundout to the right side by Coco Crisp and came around on Dustin Pedroia’s line single to center.

That was Pedroia’s third hit of the game and second three-hit game in a row. He had a three-hit night against Arizona Wednesday. Over his last five games, Pedroia is hitting .500 (11-for-22), lifting his batting average to .295. It had been as low as .260 not long ago.

Kevin Youkilis enjoyed his 27th multi-hit game of the season and first four-hit game of his career with an infield single in the second, a leadoff double in the fourth, a one-out single in the eighth and another in the ninth. Strangely, despite the four hits, he neither scored nor knocked in a run.

Finally, a two-run single with the bases loaded in the ninth by Mike Lowell gave the Sox additional breathing room. In bases-loaded situations this year, Lowell is hitting .500 (5-for-10) with 17 RBI.

Matsuzaka was sharp from the beginning, striking out the side — all swinging — in the first.

After a Lance Berkman single to lead off the second, he retired the next three hitters in a row. Through four innings, he had retired 12 of the 14 hitters he faced. His command was far sharper than his comeback start against the Cardinals, when he had the shortest outing of his major-league career.

In the meantime, the Sox had chances against Hernandez, but other than Drew, couldn’t capitalize. They stranded 10 base runners for the game.

An inning-ending double play by Lugo in the second wiped out a first-and-second, one-out opportunity. It was worse in the fourth when Youkilis doubled and Jason Varitek joined him on base with a walk.

But Hernandez got Lugo to pop to short, struck out Matsuzaka and ended the inning by getting Crisp to line to short.

smcadam@projo.com