A trio of tenured Massachusetts House Democrats have lusted after statewide office for decades, and with Sen. John Kerry’s imminent appointment to be secretary of State, they finally have their best shot.

So longtime Reps. Edward J. Markey, Michael E. Capuano or Stephen F. Lynch would jump at a temporary appointment to the seat, right?

Probably not, because it would mean giving up a safe House seat. This will be a key calculation for these three members, who must weigh the reward of the Senate seat with the risk of an appointment that would force them to relinquish their safety net.

“I doubt that any House member would give up his or her seat in order to fill the interim slot,” said Philip Johnston, a former Massachusetts Democratic Party chairman.

Gov. Deval Patrick, a Democrat, hinted last week that he’s leaning toward appointing a caretaker to the seat. But some Democrats counter that an appointee would have a leg up in a competitive general election against a Republican — likely exiting Sen. Scott P. Brown, who lost his re-election bid earlier this year.

Patrick’s comments have not stopped members of the delegation from gaming out the appointment, even if it means giving up a safe seat in the process.

The 18-term Markey, who has stockpiled $3 million in cash, will probably run only if he’s appointed to the seat first, two Democratic operatives speculated. Markey told reporters Monday morning that he’s going to give the race “serious consideration.”

But he added, “I’m going to have to weigh where I’m going to be most effective” given his post as dean of the state’s congressional delegation.

Capuano, a seven-term Democrat, will likely run in the special election regardless of whether he gets an appointment, according to two plugged-in Bay State Democrats. His office released a statement last week saying if there’s a vacant Senate seat, “Congressman Capuano would consider running for it,” but cautioned that Capuano had not lobbied for an appointment to the seat.

The cautious Lynch will look at the field to figure out whether it’s winnable — appointment or not. In any case, a special election is still several months away.

The president has not announced Kerry’s nomination yet, although several news outlets have reported his imminent plans to do so.

Under Massachusetts law, Patrick has 145 to 160 days to schedule a special election following a vacancy. But Patrick’s aides note a vacancy will not occur until Kerry completes the Senate confirmation process. That means a special primary would probably occur in April, with the general election following in June.

Any number of candidates could serve as placeholders during a special election. Democrats mentioned Vicki Kennedy, the late Sen. Edward M. Kennedy’s widow, and former Rep. Bill Delahunt as potential appointees.

The list of potential candidates in the special election is even longer.

“There are certainly a lot of potential senators running around in Massachusetts,” said David DiMartino, a Democratic consultant who worked on Kerry’s campaigns. “ A crowded primary would put the candidate with the most money, best ground game and highest name ID in the driver’s seat.”

Democrats said state Attorney General Martha Coakley could run again for the Senate, but there’s not a lot of national enthusiasm for her candidacy given her embarrassing loss to Brown in the 2010 special election. There are other previous candidates who Democrats say might want to try again, including Newton Mayor Setti Warren and City Year co-founder Alan Khazei.

Republicans see Brown as their best shot to pick up the seat, and they expect him to run. But Brown’s spokesman, Eric Fehrnstrom, called it “premature to speculate right now” in response to an email seeking comment.

If Brown doesn’t run, the shallow bench of competitive Massachusetts Republicans includes former White House Chief of Staff Andy Card, as well as former Massachusetts Gov. Bill Weld and ex-Lt. Gov. Kerry Healey.