For the third consecutive season the Patriots faced Andrew Luck and the Colts, with Luck looking to beat the Patriots for the first time in his career. The Colts overcame their inability to finish off drives like in years past, marching on a 13-play, 89-yard drive, draining 7:44 off the clock and scoring a 5-yard touchdown pass from Luck to Donte Moncrief for an early 7-0 lead. The Patriots answered, going 80 yards in 10 plays, with Brady finding Edelman for a 12-yard touchdown pass, tying the game 7-7. Afte a Colts three-and-out, the Patriots drove to Colts 22 and Gostkowski made a 39-yard field goal. After another Colts punt, Mike Adams intercepted Brady and returned it 14 yards for a touchdown. The Colts bizarrely tried an onside kick, but the Patriots recovered at their own 35. It took just four plays to score, with Blount busting off a 38-yard touchdown run, giving the Patriots a 17-14 lead early in the second quarter. The Colts countered yet again, though. Stringing together a 10 play, 80-yard drive, scoring on 3-yard touchdown pass from Luck to T. Y. Hilton, giving the Colts the lead again 21-17. The Patriots drove to the Colts 7 and Brady hit Chandler for a 7-yard touchdown, but the play was nullified on a pass interference call on Chandler. Gostkowski kicked a 35-yard field goal on the next play, giving the Colts a 21-20 lead at halftime. The Patriots took the first drive of the second half, driving 80 yards in 7 plays, scoring on Brady's 25-yard touchdown pass to Gronkowski, giving the Patriots the lead again 27-21. Four possessions later, the Colts reached the Patriots 37 and attempted a trick play on fourth down where nine players lined up wide right, while Griff Whalen lined up at center and Colt Anderson lined up as a quarterback, hoping to catch the Patriots offsides; the play failed and Anderson was sacked for a one-yard loss, leading a befuddled Al Michaels in the NBC Sports booth to mutter, "What in the world?" The Patriots declined an illegal formation penalty on the play. Taking over at the Colts 35, the Patriots needed just 6 plays, scoring on an 11-yard screen pass from Brady to Blount, increasing their lead to 34-21 a few plays into the fourth quarter. Several possessions later, the Colts drove to the Patriots 38, but turned the ball over on downs again. However, the Colts forced a quick three-and-out, and raced 85 yard in 8 plays, scoring on Luck's 18-yard touchdown pass to Whalen, with a missed extra point from Adam Vinatieri, keeping the score 34-27 with just 1:19 left. Gronkowski recovered the Colts onside kick attempt and Brady took two knees to end the game. This was the Patriots sixth straight win in the series.  The game lead tied or changed five times by halfway through the third quarter.

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