The Bills opened the regular season on the road against the first of their three divisional rivals, the New England Patriots and got off to a fast start, as on the very first play, Takeo Spikes sacked Tom Brady, causing a fumble recovered by London Fletcher-Baker for a 5-yard TD. The Patriots tied the game up at 7-7 on a 9-yard pass from Brady to Troy Brown. The Bills would regain the lead on a 53-yard FG by Rian Lindell. In the second quarter, Anthony Thomas would make the score 17-7 at halftime with an 18-yard run. However, the Bills continued their late-game struggles from 2005, as they gave up 12 unanswered points in the second-half (a 17-yard pass from Brady to Kevin Faulk, a32-yard FG by Stephen Gostkowski and a safety by Ty Warren with 8:33 remaining in the fourth-quarter), dropping the Bills to 0-1 to start the season.

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