Zverev tore ligaments in the ankle during his semi final against Rafael Nadal at Roland-Garros in June, and the world No.2 officially withdrew from the US Open on Monday night (AEST).
The 25-year-old German was on the verge of his first grand slam title two years ago at Flushing Meadows before Dominic Thiem rallied to beat him in a fifth-set tiebreaker. It was the first time a man had overcome a 2-0 deficit in the final of the event since Pancho Gonzalez did it against Ted Schroeder in 1949.
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Zverev won the Olympic gold medal in Tokyo last year and then returned to the US Open semi finals, losing to Novak Djokovic in five sets.
American Stefan Kozlov has now moved into the main draw for the tournament, which begins on Monday evening (AEST).
Reilly Opelka, who won two titles earlier this year, has also withdrawn because of injury. He reached the fourth round of the US Open last year. Fellow American Jack Sock took his place in the main draw.
Zverev has been named in Germany’s Davis Cup team for the group stages next month.
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