Police said the thieves took over the houses of two senior Northern Bank executives on Sunday, then forced the employees to help the gang gain access to the vault after the bank closed for business on Monday evening.
Assistant Chief Constable Sam Kinkaid said members of the bank employees' families had been held hostage for at least a day and were left traumatized by the ordeal.
The sum stolen "is quite considerable and may be in excess of 20 million pounds," or $39 million, Kinkaid said.
Police say more than 80 major crime gangs operate in Northern Ireland, and many gang members belong to illegal paramilitary groups. Kinkaid said Tuesday that it was "far too early to say" whether the gang behind Monday's raid had links to paramilitary groups.
Police weren't informed about the robbery until nearly midnight, six hours after the gang began clearing the safe. They said the Northern Bank employees' families suffered no wounds, but a member of one of the families was hospitalized suffering from hypothermia in circumstances that weren't explained.
The targeted safe stored money being distributed to all 95 branches of Northern Bank in Northern Ireland in the run-up to Christmas, when banks typically handle their greatest volumes of cash. Police suspect that the gang used a large truck to carry away the cash.
Northern Bank said it could not comment on any details of the raid. "However, initial indications are that affected staff are safe. This is our No. 1 priority," it said in a statement.
The group with the biggest reputation for mounting bank robberies is the Irish Republican Army, which is observing a 1997 cease-fire but continues to run a range of criminal enterprises, including cigarette and fuel smuggling. The group in the past has gained access to high-security targets by taking the families of employees hostage.
Police in May accused the IRA of taking staff hostage at Northern Ireland's biggest retail superstore, then stealing more than $7.75 million in goods loaded onto a truck.
The raid came a week after Northern Bank's owner, National Australia Bank, announced it was selling the bank to Danske Bank of Denmark in a deal expected to conclude in spring 2005.
The Guinness Book of Records said the biggest known bank robbery was that of the German central bank, the Reichsbank, in 1945, following the Nazis' defeat, in which an estimated 2.5 billion pounds at 1984 values was stolen.
Police estimated that about $65 million was stolen in 1987 from the Knightsbridge Safe Deposit Center in west London in Britain's biggest robbery.