Romney won with 39 percent of the vote. Ron Paul had a strong showing in second place with 23 percent. Jon Huntsman came in third, followed by Newt Gingrich and Rick Santorum.
Victories in New Hampshire and last week in Iowa mean Romney has a strong lead in the scramble for Republican presidential delegates. But with 1,144 needed for the nomination, there's still a long road ahead.
Romney said Wednesday morning on "Good Morning America" that he expects the upcoming primary in South Carolina to be a challenge.
"I don't know if we can win South Carolina. I was fourth there the last time I ran," said Romney. "I know it's an uphill battle, but the sendoff I got from New Hampshire last night, that's going to give me a real boost."
Texas Gov. Rick Perry skipped New Hampshire to get a head start in South Carolina. He said Tuesday's results show the race for a conservative alternative to Romney remains wide open.
Ron Paul said his second place finish shows how strong his candidacy is. Huntsman, Gingrich and Santorum all said there is ground to be made up in the South.
Now campaigning in South Carolina, Romney continues to go after President Barack Obama. But Romney's GOP rivals are trying to tear him down by painting him as a job destroyer.
"The president says he wants to transform America. I don't want to transform America, I want to restore America with the principles that made us a great nation," Romney told a crowd.
South Carolina is more blue-collar and more conservative than Iowa and New Hampshire. Unemployment is at 10 percent and people are worried about jobs, which is why his opponents are attacking Romney's resume and his years at investment firm Bain Capital, where he bought and then sold companies - sometimes creating jobs and sometimes slashing them.
"I get it about job creation. I understand the difference between venture capital and vulture capitalism," said Perry.
The so-called superPAC supporting Gingrich is spending more than $3 million to promote a documentary with images of Romney getting his shoes shined on the tarmac and stories of his large homes growing larger.
It's a strategy ripped right from the pages of the Obama team's playbook, portraying Romney as a sort of Gordon Gekko from Wall Street.
Romney has said he created 100,000 jobs at Bain, but when asked, the campaign did not give the number of how many jobs were lost.
Romney responded to the level of the attacks from his own party.
"I understand that President Obama is going to try and put free enterprise on trial. But, you know, Rick Perry and Newt Gingrich are going to be the witnesses for the prosecution. I'm not worried about that," said Romney.
The South Carolina primary is on Jan. 21 and has 25 delegates at stake, and it's winner take all. The same rule applies for Florida's 50 delegates in a later matchup.
Romney continues to be the candidate with the most cash, raising $24 million in the last quarter. He's going to need that advantage to combat the slew of negative ads and criticism from his GOP rivals, who show no signs of surrendering.