Sanford and his campaign repeatedly tried to tie Colbert Busch to Pelosi, saying that a vote for Colbert Busch would also be a vote for Pelosi, who has high negatives with Republican voters and who most likely would become House speaker again if the Democrats run the table and regain control of the chamber in next year's midterm elections.
"I've fought hard over the years to make South Carolina a better place to call home. But those efforts pale now against the larger battle for the direction of our country. Maybe that's why Nancy Pelosi and allies have spent more than a million dollars to defeat me. But this contest is bigger than them or me, it's about two different visions of how we restore America and reign in Washington spending," Sanford said, looking into the camera in a TV spot that started running district-wide last week.
Two weeks ago he even debated a cardboard cutout of Pelosi to call out Colbert Busch for not accepting more than one debate.
Sanford also repeatedly brought up the money that national Democratic groups have poured into the South Carolina race.
"What it says is, whose voice do you carry when you go to Washington D.C.?" he said in the debate with Colbert Busch, pointing to the hundreds of thousands of dollars that national Democratic groups have spent on the race.
Colbert Busch, responding to the Sanford criticism, sought to distance herself from Washington and from national Democrats.
"No one tells me what to do except the people of South Carolina's 1st Congressional District. So a victory for Elizabeth Colbert Busch is a victory for the people of South Carolina's 1st Congressional District," she told CNN Monday, adding that two-thirds of her contributions have come from within the Palmetto State.
While Sanford touted his fiscal conservative record, Colbert Bush campaigned as an independent centrist who would buck President Barack Obama. In her CNN interview, she highlighted where she doesn't see eye to eye with the president.
"I respectfully disagree with his budget," she said, adding that "we need to vote to repair" the president's health care law.
Even though they didn't support Sanford, the NRCC congratulated him Tuesday night, and said the results could prove troublesome for House Democrats in 2014.
"Democrats spent more than $1 million trying to elect a candidate who was backed by the Democrat machine, but at the end of the day, running on the Obama-Pelosi ticket was just too toxic for Elizabeth Colbert Busch," Rep. Greg Walden, NRCC chairman, said in a statement.
But national Democrats see a silver lining in Colbert Busch's defeat.
"House Republicans' outreach to women voters now has Mark Sanford as the face. Republicans now have to defend him and stand with him until Election Day," Rep. Steve Israel, DCCC chairman, said in a statement. "In this deep red Republican district that Mitt Romney won by 18 points, the fact that the Democrat made this competitive is a testament to the strength of Elizabeth Colbert Busch as a candidate and the Republican habit of nominating flawed candidates."
The congressional seat became vacant when Rep. Tim Scott, who won re-election by 27 percentage points last November, was picked by GOP Gov. Nikki Haley to fill the Senate seat of Sen. Jim DeMint, who stepped down late last year to take over as the head of the conservative Heritage Foundation.
No Democrat has held the seat in more than 30 years, and that streak still stands.