Vaughan had been in charge of ER 2015 - the company set up to deliver the 2015 Rugby World Cup - since January 2011.
A short statement announced Vaughan's departure and said a new chief executive would be appointed shortly.
ER 2015 chairman Andy Cosslett said: "Paul has been at the heart of the RFU for the past 11 years, most recently here as CEO of ER 2015, where he has laid some very strong foundations.
"We are grateful to him for all the hard work he and his team have put in to enable ER 2015 to be ready for the next phase.
"Preparations have been continuing at a good pace, the planning is completely on schedule and stakeholders are comfortable.
"With just over three years to go, now is a good time to add a fresh injection of experience to take us up to the next level.
"We are determined to make the most of this once in a generation opportunity for rugby in this country, to make this truly the best Rugby World Cup there has ever been."
Bernard Lapasset, chairman of Rugby World Cup Ltd and the International Rugby
Board, said: "On behalf of RWCL and the IRB I would like to thank Paul Vaughan for his strong contribution to developing the early foundations for the successful delivery of Rugby World Cup 2015 in England.
"Paul leaves with tournament preparations on schedule and advancing well.
"RWCL continues to enjoy a strong working partnership with England Rugby 2015 and the RFU and we look forward to working with all stakeholders to deliver an exceptional tournament of which England and the global rugby family will be proud.''
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