Robert and Grace eventually reunited, renewing their marriage vows in 2004.
The actor is notoriously private about his relationship with Grace but the pair are outspoken about their belief that their son Elliot's autism is linked to vaccinations.
Explaining how Grace believes the his son "changed overnight" after being vaccinated as a child, Robert told Today in 2017: "The vaccines are dangerous to certain people who are more susceptible...Nobody seems to want to address that, or they say they've addressed it and it's a closed issue but it doesn't seem to be.
"There are many people who will come out and say I saw my kid change overnight. I saw what happened, I should have done something and I didn't. There's more to this than meets the eye, believe me."
The Meet The Parents actor had previously been married to actress Diahnne Abbott, from 1976 to 1988.
The pair had a son, Raphael, in 1976 while the Oscar-winning actor adopted Abbott's daughter Drena from a previous relationship.
The Mean Streets star also has two children with ex Toukie Smith, twin boys Aaron and Julian.
De Niro spoke about his feelings on marriage in a 2013 interview with Katie Couric.
The star of The Godfather Part II said that the secret to a happy union involved "a lot of give and take, standing your ground, because then you keep the respect you started out with."
However, he shared some rather more cautious advice with The Independent in 2014, saying: "The only thing I would say is that if you get married, it's easier probably not to have children if you're going to split up – it makes life simpler."