Dating back to when they were based in Baltimore, the Saints have posted a 5-7 record against the Colts in the preseason, including a 21-6 loss at Jackson, Mississippi in 2006. This will be the first time the Saints have played at Lucas Oil Stadium, having previously practiced there in 2008 prior to their Week One matchup after being forced to evacuate the Gulf Coast due to Tropical Storm Gustav. The Colts and the Saints have met 11 times in the regular season, with the Saints leading 6-5, including a 62-7 win at the Mercedes-Benz Superdome on Oct. 23, 2011, which was the franchise's highest output. The Saints also defeated the Colts 31-17 in Super Bowl XLIV.
| Date | Score | Site | Attendance |
| 8/30/75 | W, 27-3 | Memorial Stadium | 60,643 |
| 8/20/76 | W, 26-20 | Memorial Stadium | 38,879 |
| 8/8/81 | W, 24-23 | Louisiana Superdome | 46,792 |
| 8/20/88 | L, 6-18 | RCA Dome | 54,117 |
| 8/12/89 | L, 7-31 | Louisiana Superdome | 57,771 |
| 8/31/90 | W, 17-14 | Louisiana Superdome | 54,796 |
| 8/17/91 | L, 28-34 | RCA Dome | 50,896 |
| 7/27/96 | L, 3-10 | Canton, Ohio | 23,376 |
| 8/21/99 | L, 7-37 | Louisiana Superdome | 41,788 |
| 8/12/00 | L, 0-17 | West Lafayette, Ind. | 20,105 |
| 8/30/02 | W, 25-21 | Louisiana Superdome | 67,247 |
| 8/26/06 | L, 6-21 | Jackson, Miss. | 44,485 |
