At the state convention on June 7, 2008, Edward O'Reilly received 22.5% of the vote, thereby granting him a spot on the September primary ballot.

Kerry had explored the possibility of seeking the Democratic nomination for president once again in 2008, a circumstance which prompted many of Massachusetts's all-Democratic House delegation, including Marty Meehan, Ed Markey and Stephen Lynch, to declare that they would run in the Democratic primary for Senate should Kerry not seek re-election.

[7] Unlike in 2002, when Kerry was re-elected against only third-party opposition, the Democratic nominee faced a Republican opponent in 2008.

The Republican candidate, former U.S. Army Delta Force officer and FBI special agent Jeff Beatty who had lost a congressional race two years earlier, was not considered a serious contender in this overwhelmingly Democratic state.

On September 16, 2008, Kerry defeated Edward O'Reilly in the Democratic primary and faced Republican Beatty in the November general election.