Florida's Supreme Court has agreed to a case review that reopens the prospect of five cigarette makers paying damages totalling $145bn (£82bn).
Tobacco firms were accused of failing to warn smokers of health risks
Tobacco shares dived after the court's decision: shares in Philip Morris owner Altria fell 8%, while RJ Reynolds' stock was down 6% on Wall Street.
A jury awarded the huge damages in July 2000 after anti-smoking campaigners brought a class action lawsuit.
The five firms successfully appealed to reduce the damages last year.
Known as the Engle case, the original lawsuit claimed damages on behalf of up to 700,000 Florida residents suffering from smoking related illnesses.
Lawyers for the plaintiffs argued that the tobacco firms had failed to issue strong enough warnings about the health risks of smoking.
The $145bn award was the biggest ever imposed in the US at the time.
But it was judged "excessive" and thrown out by the Florida appeals court in May 2003.
The scope of the Florida Supreme Court's review of case remains unclear.
The court said it "accepts jurisdiction of this case".
The five firms in the case are Philip Morris, RJ Reynolds, Loews unit Lorillard Tobacco, Brown & Williamson, which is owned by British American Tobacco, and Liggett, which is part of Vector Group.
A spokeswoman for RJ Reynolds said the company continued to believe that the appeals court "ruled correctly" in overturning the original verdict.
"We're hoping that the case will be resolved as soon as possible," she said.
Stanford University law professor Robert Rabin, who studies anti-smoking lawsuits, said he expects the damages would be reduced if they are reinstated.
But Stanley Rosenblatt, the lawyer for the plaintiffs, said he aims to see the full amount paid out.
"There's never been a hint or whisper of a settlement," he said.