The National Football League and former players who say it hid the dangers of concussion have reached a $765m (£490m) settlement, a judge says.
The NFL would pay the sum to fund concussion-related compensation, medical exams and research.
Federal Judge Anita Brody in Philadelphia announced the deal after months of court-ordered mediation.
More than 4,500 former players had sued the league, alleging it concealed the risks of long-term brain damage.
The class action accused the NFL of hiding research that had shown the harmful effects of concussions, while glorifying and promoting violent play.
Many former players with neurological conditions believe their problems stem from knocks to the head.
Helmet-to-helmet impacts are common in American football as strong, heavy and fast-moving players collide on the field of play.
Studies have linked repeated concussions with chronic traumatic encephalopathy, a disease with symptoms including memory loss and mood swings.
As part of the settlement, the NFL will neither admit liability nor that the players' injuries were caused by football and will likely not have to disclose internal files that could show what it knew about concussion-linked brain problems and when.
"This agreement lets us help those who need it most and continue our work to make the game safer for current and future players," NFL Executive Vice-President Jeffrey Pash said in statement.
"We thought it was critical to get more help to players and families who deserve it rather than spend many years and millions of dollars on litigation."
The deal is still subject to Judge Brody's approval, as well as that of the retired players who brought the lawsuit.
The plaintiffs in the case include at least 10 members of the Pro Football Hall of Fame, the family of linebacker Junior Seau, who took his own life last year, and former Atlanta Falcons safety Ray Easterling, who filed the first lawsuit in 2011 but later killed himself.
The settlement comes immediately before the start of the new season for the league.