Pence ruled out a White House bid in a letter sent to supporters that also fueled speculation he is instead planning a run for governor.
"We have been especially humbled by the confidence and support of those who believe we should pursue the presidency, but after much deliberation and prayer, we believe our calling is closer to home," Pence wrote in the letter. "In the choice between seeking national office and serving Indiana in some capacity, we choose Indiana. We will not seek the Republican nomination for president in 2012."
Pence said in the letter that he would make a decision about his future later, and would be traveling across the state in the months ahead to "learn about how Hoosiers think we might best contribute in the years ahead." Pence has a pair of public events scheduled for Friday -- a town hall meeting in Pendleton and a visit to a high school in Muncie.
While there is no official word yet on whether he'll run for Indiana governor, many in political circles assumed that would be the case since he stepped down last year from his House leadership position.
"I am convinced he is now going to run for governor," said Mike McDaniel, a former state Republican chairman.
The 51-year-old Pence is a darling of social conservatives and often describes himself as "a Christian, a conservative, and a Republican, in that order." He had made multiple trips to states that host early presidential primary contests.
McDaniel said the decision not to run must have been difficult.
"He had a lot of people around the country who were eagerly pushing him toward that decision to run for president," he said.
The congressman's future has been the subject of speculation since he resigned the No. 3 GOP House leadership slot after winning sixth term in November.
One of his party's strongest advocates for conservative policies, Pence is among the GOP's most outspoken critics of President Barack Obama. In September, Pence finished first in a straw poll of social conservatives who were asked to name the person they'd like to see as the 2012 nominee.
But if Pence had entered the presidential contest, he would have faced an uphill climb. Few Americans have heard of him and better known potential Republican candidates already have organized fundraising operations.
The field for Indiana governor is wide open, and Pence is most prominent Republican discussed as a candidate to replace GOP Gov. Mitch Daniels, who can't run for a third term and also is considering whether to enter the 2012 presidential campaign.
Pence is from Columbus and was an attorney before running unsuccessfully for Congress against Democrat Phil Sharp in 1988 and 1990. He then was president of the Indiana Policy Review think tank and a radio talk show host before running for Congress again in 2000 after Republican David McIntosh gave up the seat for an unsuccessful run for governor.