Coming off a bad loss to the Philadelphia Eagles, the Jaguars looked to rebound against their division rival Indianapolis Colts. Indianapolis scored on its first possession as running back Joseph Addai ran it in from two yards out to make the score 7-0 Colts. After two touchdown runs by David Garrard and Maurice Jones-Drew, the Jaguars took the lead in the second quarter, 14-7. Their lead didn't last very long as quarterback Peyton Manning threw a seven-yard touchdown pass to tight end Dallas Clark, tying the game at 14 heading into halftime. The Jaguars regained the lead in the third quarter with Garrard finding tight end Marcedes Lewis for a fifteen-yard touchdown pass. Jacksonville took the lead 21-14. Once again, the Colts responded when Addai scored on a two-yard touchdown run tying the game at 21. With 2:13 left in the game, Garrard completed it to Maurice Jones-Drew for an eight-yard touchdown pass and the Jaguars took a 28-21 lead. That was enough time for 4 time MVP Peyton Manning, however as he hooked up with wide receiver Austin Collie for a one-yard touchdown that appeared as if it would send the game into overtime. The Jaguars got the ball back with 0:42 left on the clock, with the game tied. After a few short plays, the ball was at the Jacksonville 37-yard line with 0:33 left to play. Garrard then threw a deep pass to wide receiver Tiquan Underwood who caught it along the left sideline with 0:18 remaining in the game. Two plays later, kicker Josh Scobee lined up for a fifty-nine-yard field goal to win the game. Scobee's kick set a record for longest field goal in Jaguars franchise history.

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