Andrew Luck threw for two TDs, Vick Ballard ran for another and Deji Karim scored on a 101-yard kickoff return to give the cancer-beating coach a 28-16 win over AFC South champ Houston in his return to the sideline.
Those who thought Pagano might take it easy in his first game back at the helm of the wild-card Colts since starting the first of three rounds of chemotherapy Sept. 26 were wrong.
Pagano spent the pregame warm-ups hugging friends such as offensive coordinator and former interim coach Bruce Arians, and Texans defensive coordinator Wade Phillips. During the game, he was the same old guy. Pagano took his customary linebacker stance, hands on bended knees, signaled touchdowns when the Colts scored, patted players on their helmets and gestured for flags to be thrown. He even sprinted a few times.
Fans gave Pagano a standing ovation after a 1-minute video was shown on the stadium's two Jumbotrons just before kickoff.
But Pagano's players wanted to welcome back another way: with a victory celebration. Indy (11-5) did everything it needed to get it Sunday, perhaps damaging the Texans' playoff seeding, too.
The Colts play at Baltimore in the wild-card round next weekend. The slumping Texans (12-4) have lost three of their last four and won't know their AFC seeing until after Denver and New England finish later Sunday.
Indy prevented J.J. Watt from getting any closer to Michael Strahan's NFL sacks record (22½). Watt finished the season with 20½.
Luck broke Peyton Manning's rookie record for completions and moved into third all-time among rookies with 22 TD passes. He finished 14 of 28 for 191 yards, giving him 339 completions this season.
Of course, the Colts gave Pagano a game ball, then watched him lead an impromptu dance in the locker room, including a do-si-do with team owner Jimmy Irsay.
It didn't take long for the Colts to assert themselves in this emotional environment — or to swing the game when the Texans took their only lead. Shayne Graham made a 37-yard field goal with 5:22 left in the third quarter, but that lead lasted all of 12 seconds.
Karim fielded the ensuing kickoff 1 yard deep in the end zone, found a seam in the middle of the field and never slowed until he reached the opposite end zone to make it 21-16. Pagano patted him on the helmet after the longest kickoff return since the Colts moved to Indy in 1984.
Then, facing third-and-23 from the 30, Luck threw a perfect strike through a narrow window, hitting T.Y. Hilton in stride for a 70-yard TD to make it 28-16.
On a day the Texans mostly settled for field goals, that's all the Colts needed.
Luck masterfully led the Colts 75 yards in 13 plays on the game's opening possession, prompting Pagano to call for a defensive pass interference call on third-and-goal. Pagano also flung his arms into the air when Luck hooked up with Coby Fleener for a 1-yard score.
Graham made a 51-yard field goal late in the first quarter and 37-yarder early in the second.
But after Matt Schaub's underthrown pass was picked off by Vontae Davis and returned 26 yards to the Houston 39, Luck went back to work. He found Hilton for a 17-yard completion before Ballard plunged in from the 1 to make it 14-6.
Pagano was even on the minds of the Texans.
Houston opened the second half with its only touchdown when Arian Foster broke through a hole for a 13-yard TD run. Instead of doing his trademark bow, though, Foster ran through the end zone and tapped the (hash)Chuckstrong sign hanging on the wall. That made it 14-13.
Schaub finished 24 of 36 for 275 yards with two interceptions and no touchdowns. Foster ran 16 times for 96 yards.