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Already the King of Clay, the Spaniard has been a master of the Flushing Meadows hardcourts this New York fortnight but had to dig mighty deep to beat the Russian 7-5 6-3 5-7 4-6 6-4 on Sunday (local time).
A routine end to the Flushing Meadows fortnight looked on the cards when Nadal went up two sets and a break up, but it turned into a near five-hour thriller as Medvedev staged a comeback that left the Spaniard shaken and Arthur Ashe Stadium buzzing.
Not once since 1949 had a player come back from two sets down to win the US Open final but the tall Russian, cheered loudly by a crowd that booed him mercilessly earlier in the week, came mighty close.
Nadal needed three championship points to finally kill off his 23-year-old opponent and let out a mighty roar as Medvedev's final return sailed long before falling on his back to soak up the cheers.
Already the King of Clay the Spaniard has been a master of the Flushing Meadows hardcourts this New York fortnight, dropping just three sets on way to the final.
The 33-year-old lefthander became the second oldest US Open champion in the professional era behind Australian Ken Rosewall, who was 35 when he lifted the title in 1970.
Medvedev arrived at his first Grand Slam final as the hottest player in men's tennis, riding the momentum from reaching four consecutive finals, but it was not enough to carry him to a maiden major title.
Nadal was not exactly holding a cold hand either, the Spaniard riding a 10 match win streak going 26-1 in his last five events.