Following their win over the Chargers, the Patriots flew to Orchard Park, New York for an AFC East duel with the Buffalo Bills. The Patriots grabbed the lead in the first quarter, with quarterback Tom Brady throwing two touchdown passes - a 14-yarder to wide receiver Wes Welker and a 1-yarder to tight end Rob Gronkowski. The Patriots added to their lead in the second quarter, with Brady connecting with Rob Gronkowski on a 26-yard touchdown pass. The Bills responded, with quarterback Ryan Fitzpatrick throwing an 11-yard touchdown pass to wide receiver Steve Johnson, followed by a 42-yard field goal by placekicker Ryan Lindell. The Bills narrowed the Patriots' lead in the third quarter, with a 3-yard touchdown pass from Fitzpatrick to tight end Scott Chandler. The Patriots increased their lead, with a 23-yard field goal by placekicker Stephen Gostkowski. The Bills tied the game in the fourth quarter, with a 1-yard touchdown run by running back Fred Jackson, then grabbed a 31-24 lead when cornerback Drayton Florence returned a Brady interception 27 yards for a touchdown. The Patriots tied the game, with a 6-yard touchdown pass from Brady to Welker. However, the Bills got the last possession, as Lindell nailed a 28-yard field goal as time expired, snapping the Patriots' 15-game winning streak against the Bills.

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