Giampaolo Pazzini came close to giving the visitors the lead in the sixth minute when he was played in by Kesuike Honda and chipped the ball over the on-rushing keeper, but his attempt was headed off the line.
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Milan were dominating the early exchanges and opened the scoring in the 12th minute. Adel Taarabt saw his header from Adil Rami's cross spilled by Angelo da Costa, and he reacted quickly to poke the rebound into the net.
Honda was the next to threaten for the Rossoneri midway through the first half when he was picked out on the edge of the box by Kevin Constant, but he could not get enough power on his low strike to beat the keeper.
Pazzini came close to adding a second at the end of the half when he saw his header saved by the keeper.
Milan continued to dominate after the break and doubled their lead in the 58th minute, when Rami headed in at the back post after Da Costa had failed to claim a cross from the right wing.
Sampdoria's hopes of salvaging anything took a blow in the 72nd minute when Maxi Lopez was shown a red card for arguing with the referee.
Amelia was proving hard to beat in the Milan goal and he denied Eder from point-blank range after the Brazilian had flicked on Renan Garcia's low cross.
Rami came close to adding a third goal in the final minute when he directed a header straight at the keeper, as Milan saw out the game to claim a second consecutive league win.