Tisei ran for the United States House of Representatives in 2012, narrowly losing to seven-term Democratic incumbent John F. Tierney by 1.2%.

A high school visit to the Massachusetts State House gave Tisei "the political bug.

"[4] In 1982, Tisei was an intern at the White House at the domestic office of Vice President George H. W.

[6] In 1984, Tisei ran for the open 22nd Middlesex district seat of the Massachusetts House of Representatives.

Running as a Republican, Tisei defeated Democratic candidate Donald Flanagan, of Wakefield 11,189 to 8,263 and took office the following year.

[27][28] On July 28, 2009, Tisei was named the campaign chair for Charlie Baker's 2010 gubernatorial run.

On November 23, 2009, Baker named Tisei as his running mate, and thus as a candidate for lieutenant governor.

[30] The newly redrawn Massachusetts's 6th congressional district remained largely the same, but added Billerica, Tewksbury, and Andover.

[31] This was a swing district where Scott Brown got 58% of the vote in January 2010 and where Baker/Tisei got 50% in the November 2010 gubernatorial election.

David Scharfenberg of The Boston Globe speculated that the payments were to support his campaign for Congress.

The Tisei campaign has noted that the payments were all made prior to his official declaration of candidacy for Congress and that they were for activities in support of a potential run for state-level office.

It was widely thought that he would face incumbent Congressman John F. Tierney in a rematch from the 2012 race.

But on September 9, Tierney became the fourth member of the U.S. House of Representatives to lose a primary election in the 2014 cycle.

[37] Tisei was notably endorsed by Marisa DeFranco, a Democrat who unsuccessfully ran for United States Senate in the 2012 election.

[38] Tisei boycotted the Republican state convention because of the "socially conservative platform the party adopted.

"[40] He was endorsed by the Gay and Lesbian Victory Fund[41] but was soundly beaten by Moulton in the general election, by 149,638 votes (54.97%) to 111,989 (41.13%).