Steve Hilton, a former No 10 adviser and a close ally of the Prime Minister, says the UK must vote to leave the EU.
Hilton blasted the EU as "anti-market, stifling innovation and competition with its statism, corporatism and bureaucracy", in a Daily Mail article.
"These are issues that a reformed EU might address," he said.
"I could certainly live with an imperfect EU that nevertheless showed some willingness towards dispersing, rather than centralising, power.
"But it is perfectly obvious to everyone, including Mr Cameron, that no such reorientation will ever be countenanced."
Hilton slammed the EU for its "arrogant and dismissive treatment of Britain's relatively modest demands" during negotiations over the past year, and also warned that if the UK votes in favour of staying it will lose its leverage within the union.
Look how they treated a British Prime Minister armed with the threat of Brexit. Can you imagine how they would treat a future PM without such a powerful card to play?
While he acknowledged that there would be some risk involved in a Brexit, Hilton stated that it would be the right choice.
"A decision to leave the EU is not without risk, but I believe it is the ideal and idealistic choice for our times," Hilton said.
"Taking back power from arrogant, unaccountable, hubristic elites and putting it where it belongs. In people’s hands."
Hilton's call for a Leave vote follows a warning from chancellor George Osborne that a Brexit could trigger a recession.