The only daughter and eldest child of the late Senator Edward Kennedy, Kara, has died of heart failure aged 51, her brother Patrick has said.
The former TV producer was in remission after having a malignant tumour on her lung removed in 2003. She had been weakened physically, he said.
In recent years, Kara Kennedy Allen worked for a charity involved in providing arts opportunities for the disabled.
Senator Kennedy died in August 2009.
She received the Presidential Medal of Freedom on his behalf from President Obama just 13 days before her father's death.
She is survived by brothers Patrick, a former congressman from Rhode Island, and Edward Junior, a lawyer and investment banker, her mother Joan Kennedy and a teenage son and daughter.
Reports say that she died after her daily work-out at a health club in the Washington DC area.
Patrick Kennedy said his sister loved to exercise but that the cancer treatment "took quite a toll on her and weakened her physically".
"Her heart gave out," he added. "She's with dad