Super Bowl champions Indianapolis began the new NFL season with a 41-10 home win over the New Orleans on Thursday.
Peyton Manning completed 18-of-30 pass attempts for 288 yards and three touchdowns, including two for New Orleans-born receiver Reggie Wayne.
"This is just one game, it takes 16 games," said Manning. "It sure was a good start but that's all it is."
He is trying to become the first player in NFL history to toss 25 TD passes in 10 consecutive seasons.
The Colts got off the mark with Manning throwing a 27-yard touchdown pass to receiver Marvin Harrison.
It marked the 107th time Manning and Harrison, the most lethal quarterback-receiver partnership in NFL history, had combined for a TD.
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The Saints, who came within a game of meeting Indianapolis in last season's Super Bowl, made a fight of it early on.
Cornerback Jason David recovered a fumble by Wayne and returned it for the score and both teams traded field goals to end the half at 10-10.
The Colts offence shifted into top gear in the third quarter with Manning engineering a pair of drives capped off by TDs from Joseph Addai and Wayne to surge 24-10 ahead.
An Adam Vinatieri field goal opened the fourth quarter before Manning found Wayne in the end zone again, then Matt Giordano intercepted Saints QB Drew Brees and returned the ball 83 yards to complete the rout.
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