With Ortiz swinging the bat well heading to Target Field, the surging Red Sox seek a seventh straight win in Minnesota on Tuesday night in the opener of a three-game series.
Ortiz battled injuries and inconsistent play after breaking in with Minnesota in 1997, and the Twins released him once knee problems limited him to 125 games in 2002.
Minnesota's trash has became Boston's treasure since the Red Sox (19-18) signed him before the 2003 season. Ortiz hit .288 with 31 homers and 101 RBIs in his debut Boston season before making the first of nine All-Star appearances the following year.
On Saturday, Ortiz hit his 380th home run as a member of the Red Sox to break a tie with Dwight Evans on Boston's all-time list. He now needs just three more to draw even with Jim Rice for third.
"It means I'm getting old," Ortiz told the team's official website. "You play the game and the last thing you think about is having your name mentioned with those guys. But once it happens, it's an honor."
The 2013 World Series MVP has hit 15 of those homers in 204 at-bats against his former team. His .333 average versus Minnesota (17-19) is the highest of any AL opponent - except Houston, which joined the league last season.
Ortiz also has batted .543 with five homers and 15 RBIs to help Boston win eight of its last nine road games in the series.
While he's gone 8 for 19 with a homer over his last five overall, Ortiz has one hit - a home run - in seven career at-bats against Minnesota's Ricky Nolasco (2-3, 5.64 ERA).
Following a shaky start to the season, the right-hander has had two straight quality starts after holding Cleveland to three runs with a season-high nine strikeouts over six innings of Wednesday's 4-3 road loss.
Nolasco has gone 2-2 with a 5.24 ERA in four career starts versus Boston, but he threw a two-hitter against the Red Sox in a 2-0 win Aug. 23 while with the Los Angeles Dodgers.
Shane Victorino went hitless in four at-bats in that contest, leaving him 6 for 40 with nine strikeouts all-time versus Nolasco. The right fielder is 8 for 22 with two homers in his last five games against the Twins.
Dustin Pedroia went 2 for 4 with a home run Sunday as the Red Sox won 5-2 in Texas for their sixth victory in eight games. He's batted .375 with two homers over that stretch and is hitting .414 in 22 career games in Minnesota.
Boston's Felix Doubront (1-3, 5.09) hopes to build on his promising performance last Tuesday when he surrendered one run over 5 1-3 innings in a 4-3 win in 12 over visiting Cincinnati.
The left-hander, however, has allowed 11 runs and 19 hits over 10 1-3 innings in two career starts against the Twins.
Joe Mauer, who is 2 for 4 with a double off Doubront, is expected to return to first base after serving as DH the past two games because of back stiffness. He's hitting .370 over his last six meetings with the Red Sox.
Josmil Pinto had his third straight two-hit game Sunday as Minnesota took two of three from first-place Detroit with a 4-3 road win.