Coming off their win over the Eagles, the Saints flew to Ralph Wilson Stadium for a Week 3 interconference duel with the Buffalo Bills. New Orleans would make an immediate impact in the first quarter with running back Lynell Hamilton's 1-yard touchdown run. The Bills would answer in the second quarter when a fake field goal attempt, punter Brian Moorman would complete a 25-yard touchdown pass to defensive end Ryan Denney. The Saints would close out the half with kicker John Carney's 27-yard field goal. After a scoreless third quarter, New Orleans would take control in the fourth quarter with running back Pierre Thomas' 34-yard touchdown run, Carney's 35-yard field goal, and Thomas' 19-yard touchdown run.

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