The world number three had been due to face Stefanos Tsitsipas in the quarter-final in Rome on Friday.
A statement on the tournament’s website said: “Roger Federer has just phoned the ATP supervisor and tournament director to announce his retirement due to a problem with his right leg.”
Federer, whose only French Open title came a decade ago, had been hoping to build up some momentum on clay courts ahead of his first appearance at Roland Garros since 2015.
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