"I'm undecided, and I'm still in the same boat as when I came," said Zander Morales, a hospital worker in Des Moines after he attended a rally on Monday for Mr Paul, the US congressman from Texas. "I'm not sure what I'm going to do."
Republican voters in Iowa gather for the caucuses at more than 800 sites across the state beginning at 7pm EST (midnight GMT). Results should begin to come in within a few hours.
The event is the culmination of months of campaigning in Iowa, and starts a frenzied schedule that will include a half-dozen debates in January and three more state contests – on Jan 10 in New Hampshire, Jan 21 in South Carolina and Jan 31 in Florida.
The stakes are high for each of the six candidates competing in Iowa. Mr Romney, the former governor of Massachusetts, is aiming for a win that could ease persistent conservative doubts about his record and propel him toward clinching the nomination early.
Struggling rivals like Texas Governor Rick Perry and US Representative Michele Bachmann are fighting for at least a fourth-place finish that could keep their flickering White House hopes alive.
And Newt Gingrich, the former US House Speaker who led the race just weeks ago, aims to end his slide and prove he can make a comeback.
Mr Santorum was trying to consolidate fractured religious and social conservatives in Iowa and emerge as the leading conservative alternative to Romney.
But Mr Perry, Mr Paul and Mr Romney criticised Mr Santorum for backing costly spending bills when he served in the Senate, hoping to halt his rise in the final hours of the campaign.
"He spends too much money," Mr Paul told CNN.
Iowa's nominating contest has a spotty track record of picking winners, but has traditionally cleared the presidential field of losers and elevated surprise contenders.
Polls show Mr Romney performs best of all the Republicans in head-to-head matchups with Mr Obama in a general election campaign certain to focus on the economy and high unemployment.
But some voters in Iowa were torn between their urge to reclaim the White House from Obama and their search for a candidate who best meets their conservative principles.
Mr Santorum supporter Peggy Greenfield of Clive, Iowa, said she was drawn by his "consistent family values" and foreign policy knowledge.
"When people see the momentum he has going it gives them the courage to go out and caucus for him," she said.