The Walk the Line star, 42, seemed to have partied hard while helping friend Aniston celebrate turning 50 (this Monday).
Witherspoon, who tottered around in a mini dress and black high heels all night, shocked onlookers with her hard tumble.
The embarrassing incident began when the actress looked red-faced as she exited the party.
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She grabbed a glass handrail for support as she and such huge stars as George Clooney, Sandra Bullock, Courteney Cox, Gwyneth Paltrow, and Ellen DeGeneres left the bash at the Sunset Tower hotel in West Hollywood.
Witherspoon appeared bleary-eyed and suddenly lost her balance, falling down the staircase, while her bodyguard and an assistant looked on. The Big Little Lies star wound up in a heap at the bottom of the stairwell!
A hotel worker came to her aid; Witherspoon got up and walked to her chauffeur-driven car.
Witherspoon and Aniston will be co-stars on the upcoming Apple TV series Top Of The Morning, about the cast and crew of a morning news show.
he blonde beauty's fall isn't the first time she's been embarrassed. In 2013, Witherspoon and her husband Jim Toth were both arrested in Atlanta, Georgia. Witherspoon was busted on a disorderly conduct charge according to a police report obtained by Radar at the time. The actress was handcuffed after disobeying repeated instruction from the arresting officer to stay inside the vehicle.
Toth faced a DUI charge after driving in the wrong lane. "Do you know my name?" Witherspoon was quoted as asking the state trooper who stopped the couple. According to the arrest report, she also said, "You're about to find out who I am" and "You're about to be on national news."
Witherspoon publicly apologized afterwards, saying in a statement, "I clearly had one drink too many and I am deeply embarrassed about the things I said. It was definitely a scary situation and I was frightened for my husband, but that is no excuse. I was disrespectful to the officer who was just doing his job. I have nothing but respect for the police and I'm very sorry for my behavior."
She later pleaded no contest to obstruction and was required to pay court costs. Toth pleaded guilty to misdemeanor DUI, was ordered to perform 40 hours of community service and attend an alcohol education program, plus pay a $600 fine.
Radar recently learned that Witherspoon has finalized negotiations to reprise her role as lovable diva Elle Woods in Legally Blonde 3 – for a whopping $12 million.
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