US drugs giant Merck is vowing to fight a potential wave of thousands of lawsuits over the painkiller Vioxx, once taken by 20 million people.
The jury accepted that Vioxx killed Robert Ernst
A widow in Texas won $253.4m (£141.07m) damages after a jury accepted that her husband had been killed by the drug.
The verdict could clear the way for some 4,200 other cases involving Vioxx, which raises the risk of heart attacks or strokes if taken for a long period.
Merck denies responsibility and says it will appeal against the Texas ruling.
"We don't believe they (plaintiffs) met their burden of proof," said Merck lawyer Jonathan Skidmore in a statement.
"[The appeal will] be based on the fact that we believe unqualified expert testimony was allowed in the case [and] there were expert opinions that weren't grounded in science."
The firm insists it acted responsibly throughout the drug's life, testing it thoroughly and pulling it from the market once the problems emerged.
And in the specific case of Mr Ernst, Merck says his death was caused by other health problems, not by Vioxx.
But widow Carol Ernst's lawyers insisted the drug was to blame, and had stayed on the market for months after it was known to be dangerous.
US government research has estimated that 27,785 heart attacks or deaths may have been caused by the drug between its approval in 1999 and its withdrawal by Merck last year.
The next courtroom tests for Vioxx will come in New Jersey, in a trial starting next month, and in New Orleans in late November.
As well as thousands of pending cases in the US, there are at least 150 potential cases in the UK and 100 in Australia.
Some analysts believe the company could end up having to pay out $18bn if it loses future cases.
Shares in Merck fell 7% on Friday after the Texas verdict was announced.
Some Wall Street analysts predict the firm's woes may drag on for years.
"It will cost them at least $1bn a year for the next 10 years," John LeCroy, an analyst at Natexis Bleichroeder, told Reuters news agency.
The Texas jurors made the multi-million dollar award to Mrs Ernst to cover a combination of her husband's lost pay as a Wal-Mart produce manager, mental anguish, loss of companionship and punitive damages.
Mrs Ernst has expressed her relief at the verdict.
"In the four years that I knew and loved Bob, I went to a lot of his marathons, his triathlons. This has been my run for Bob," she said after the verdict.
Her lawyer, Mark Lanier, said the high damages were necessary to make an example of Merck, which he accused of putting profit before safety.
"You have got a company worth billions and billions and billions of dollars," he said.
"If you write down $10m, Merck laughs. It's a rounding error. It's got to be over $100m or they won't even pay attention."
However, correspondents say the amount of damages is likely to be reduced on appeal even if the firm's liability is confirmed, as Texas law places an upper limit on the percentage amount of punitive damages which can be awarded by a jury.