Johnson & Johnson has been ordered to pay $4.69bn (£3.6bn) to 22 women who alleged the pharmaceutical company's talc products contain asbestos that caused cancer.
A Missouri jury ruled in favour of the women after a six-week trial and awarded $550m in compensation and $4.14bn in punitive damages – the largest payout the company has faced.
J&J is battling another 9,000 cases. The company, which has successfully overturned previous cases, denies its talc products contain asbestos that caused ovarian cancer and plans to appeal the case.
"Johnson & Johnson is deeply disappointed in the verdict, which was the product of a fundamentally unfair process," it said in a statement.
"Every verdict against Johnson & Johnson in this court that has gone through the appeals process has been reversed and the multiple errors present in this trial were worse than those in the prior trials which have been reversed."
The company claims decades of studies, including one by the US Food and Drug Administration, found its talc-based products, including J&J's Baby Powder, to be safe.
The women and their families allege J&J knew its talc contained asbestos since the 1970s.
"For over 40 years, Johnson & Johnson has covered up the evidence of asbestos in their products," the plaintiffs' lawyer Mark Lanier said in a statement.
"We hope this verdict will get the attention of the J&J board and that it will lead them to better inform the medical community and the public about the connection between asbestos, talc, and ovarian cancer," he said.
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"If J&J insists on continuing to sell talc, they should mark it with a serious warning," Lanier said.
A previous ruling in 2017 by a California jury awarded $417m but that was later overturned on appeal. Several other legal challenges by J&J are pending.