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This was their eighth meeting in Rome, and their fifth in the final. Nadal now leads Djokovic 5-3 in Rome, and 3-2 in finals there.
The Serbian will meet either five-time Madrid champion Rafael Nadal, the world number two, or Stefanos Tsitsipas in Sunday's final.
There was a brief loss of focus when Djokovic was broken to love midway though the second set but he was quickly back in the groove to move two sets ahead.
The world No. 1 took one hour and 32 minutes to defeat the rising Greek star.
Djokovic moved 6-3 ahead and, after the final point had to be replayed following a Hawkeye challenge
No matter that Novak Djokovic is arguably the best returner the game and has an engaging personality, there is only so much love to go around.
It proved only a minor inconvenience, though, as the four-time winner surged through 7-5, 6-7 (5), 6-1, 6-4.
Half an hour later he had lost 10 games in a row and the match was effectively over as Djokovic, relentless with his accuracy, went on to triumph 6-4, 6-0, 6-2.
The match turned on an amazing 45-shot rally in the sixth game of the third set, which Djokovic won to break serve – and from then on he took total control.
After a few early wobbles Djokovic triumphed 6-3, 7-5, 6-3 as, perhaps already buoyed by the presence of new coach Goran Ivanisevic.
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