Nasa had deemed Apophis to be one of the most dangerous asteroids to Earth after its discovery in 2004.
Close calls in 2029 and 2036 were predicted and later ruled out. A slight threat still remained for 2068.
But now Nasa has dismissed that threat based on new analysis of the asteroid.
"A 2068 impact is not in the realm of possibility any more, and our calculations don't show any impact risk for at least the next 100 years," Davide Farnocchia, a scientist who studies near-Earth objects for Nasa, said in a statement on Friday.
Named after the ancient Egyptian god of chaos and darkness, Apophis is estimated to measure 340m (1,100ft) across - about the length of three UK football pitches.
The asteroid recently made a distant flyby of Earth on 5 March, passing within 17 million km (10 million miles) of the planet.
Astronomers were able to use radar observations to refine their estimate of the asteroid's orbit around the Sun, allowing them to confidently rule out any impact risk in 2068 and long after.
"When I started working with asteroids after college, Apophis was the poster child for hazardous asteroids," said Mr Farnocchia. "There's a certain sense of satisfaction to see it removed from the risk list."
He said Nasa was "looking forward to the science we might uncover during its close approach in 2029".
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