Zanardi found a seat back in Cart in 2001, driving for a team set up by his former Ganassi engineer Mo Nunn.
He was leading the race at Germany's Lausitzring oval held just four days after the 11 September attacks in the US when the accident that changed his life took place.
Exiting the pits in the closing stages of the race, Zanardi made a mistake and spun on to the track. Canadian Alex Tagliani hit Zanardi's car broadside, at close to 200mph, tearing off its nose.
The crash was like a bomb going off, and in the aftermath Zanardi's noseless car lay across the track, a river of blood flowing from it.
His heart stopped seven times. He survived for nearly an hour with less than a litre of blood. He was saved by the expert intervention of the medical team, led by Dr Steve Olvey.
Talking about regaining consciousness in hospital in Berlin eight days after the accident, Zanardi said: "I surprised myself feeling, or sensing, the highest joy I have ever had in my life. The pain was incredible. I cannot describe it. But I was alive. Who cares about my legs? I am alive. It was the most natural thing for me to focus on what I had left."
It was the end of his career in single-seater racing, but he set upon an extensive rehabilitation programme and was fitted with prosthetic limbs.
In 2003, he was given a run in a Cart car fitted with hand controls back at the Lausitzring, symbolically completing the 13 laps remaining from the race he never finished two years before.
He lapped quickly enough to qualify for the race, and that encouraged him to believe he could make a comeback to motorsport. He did a deal with BMW to provide him with a car fitted with hand controls in the World Touring Car Championship, where he competed for five seasons from 2005-9, winning four races.
Although now into his 40s, Zanardi had already embarked on another challenge that would lead to his greatest achievements.
In 2007, he finished the New York City marathon fourth in the hand-cycle class after just four weeks of training. This became Zanardi's main focus and as the years passed by, his success grew.
In 2011, he won the New York Marathon. Then, at the 2012 London Olympics, he took gold medals in the road race and the road time trial, following up with another double in Rio De Janeiro four years later, this time twinning the road time trial with the road team relay.
In effect, he dominated the sport for seven years, adding a total of 12 world championship gold medals from 2013-19.
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