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Jayawardene top-scored with an unbeaten 71 and skipper Sangakkara made a brisk 55 as Sri Lanka passed India's 245 with nine balls to spare in the day-night match.
The duo also upstaged India's Suresh Raina, who cracked a gutsy 106 under pressure to prop up the innings.
"I always say we have got match-winners in the side and when it mattered today every one of them fired. It was a great start and all credit to the bowlers," said Sangakkara, who was named man of the series.
India were a bowler short when paceman Ashish Nehra left the field with an injury soon after having opener Upul Tharanga caught by Virat Kohli at second slip with his third delivery.
Opener Tillakaratne Dilshan (49) and Sangakkara dominated the Indian attack with aggressive shots, adding 93 for the second wicket.
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India's spinners brought their side back into the game, removing well-set Dilshan, Sangakkara, Thilan Samaraweera (27) and Thilina Kandamby (18) to reduce Sri Lanka to 189-5. Off-spinner Harbhajan Singh