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.
Bologna-born 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.”
Zanardi won the H4 time trial and H4 road race at London 2012 and was selected to be the Italy team’s flagbearer at the closing ceremony.
At Rio 2016, he won gold in the H5 time trial and relay.
The International Paralympic Committee called Zanardi “a pioneer, icon and legend of the Paralympic movement”.
It added: “His performances were truly out of this world, engaged new fans to the Games, and showed the world that anything is possible.
“The iconic picture of him raising his handcycle above his head in victory at London 2012 will go down in history as one of the great sporting images. He will be remembered forever.
“Our thoughts are with his friends and family at this difficult time.”
Formula 1 boss Stefano Domenicali described Zanardi as “an inspirational person, as a human and as an athlete”.
“He faced challenges that would have stopped anyone, yet he continued to look forward, always with a smile and a stubborn determination that inspired us all,” added Domenicali.
“While his loss is profoundly felt, his legacy remains strong.”
