Mark Ingram vs. Bills LBs
New Orleans Saints receiving back Alvin Kamara will be a tough matchup for the Buffalo Bills' LBs in coverage but it all starts with Ingram. If the Bills can't limit the Saints' run game, they have no chance against Drew Brees' passing. The Saints like to run inside zone plays, double-teaming at the point of attack. The Jets did a lot of that with success last week. Adolphus Washington must be stout against double-teams. New Orleans ranks seventh in rushing at 122 yards a game. Since they're playing with a lead more, the Saints are running more (44 percent to 36.5 percent last year). Brees is on pace for 550 attempts, which would be his fewest since 2009.
LeSean McCoy vs. Saints LBs
The best way to contain a great quarterback is to keep him on the sidelines. The Bills need to try to get McCoy in space against linebacker A.J. Klein and Craig Robertson. The Saints have allowed nine 20-plus rush gains, tied for most in the NFL. The New Orleans defense ranks 19th in rush yards and 29th in yards per rush allowed. Saints defensive coordinator Dennis Allen is known for mixing things up. He might throw a few Jets-like 3-4 fronts at the Bills just to keep the offensive line off balance. Look for the Bills to try to isolate McCoy in coverage on Klein, as well.
Tyrod Taylor vs. Saints DBs
It's unrealistic to think the Bills' defense is going to shut down the Saints' attack. Taylor and the passing game must be productive. No. 2 cornerback Devin Breaux is out for the year. Ken Crawley, undrafted in 2016, is a big athlete who has played well in his place. But he's still young. The Saints have relied on safety Kenny Vaccaro to play slot corner, but he's hurt (groin), too, and could be out. Can the Bills make the Saints pay for their blitzing tactics? With backup secondary men on the field, look for the Bills to try some stack releases to create confusion.