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It is the second time in three years that the Australian, who has now moved back up to the world number one ranking, has won the tournament.
Oosthuizen took the early advantage in the final by winning the opening hole, but Day overtook him and was three holes up at the turn.
The 28-year-old, who won the Arnold Palmer Invitational last week, sealed a 5&4 triumph after shooting birdies on the 13th and 14th holes.
McIlroy took on Rafael Cabrera-Bello for third place, but he ended up losing 3&2 in the playoff.