Zanardi returned to motorsport after his crash, winning four times for BMW in the World Touring Car Championship from 2005-09.
In addition to his handcycling success at the Paralympics, he became a 12-time world champion and won the men’s para-cycling race at the New York marathon in 2011.
Zanardi suffered serious head injuries in 2020 when he lost control of his handbike during a road race in Tuscany and crashed into an oncoming truck.
Formula 1’s governing body the FIA said, external Zanardi’s “journey from life-changing accident to Paralympics gold medallist made him one of sport’s most admired competitors and an enduring symbol of courage and determination”.
Italian Prime Minister Giorgia Meloni said, external her country had lost “a great champion and an extraordinary man, capable of turning every trial of life into a lesson in courage, strength, and dignity”.
She added: “Alex Zanardi knew how to get back in the game every time, facing even the toughest challenges with determination, clarity, and a strength of spirit that was truly exceptional.
“With his sporting achievements, with his example, and with his humanity, he gave all of us much more than a victory: he gave hope, pride, and the strength to never give up.
“On behalf of myself and the government, I extend my heartfelt thoughts and the sincerest closeness to his family and to all those who loved him.
“Thank you for everything, Alex.”