In Week 16, against the playoff-bound Arizona Cardinals, Cassel led the Patriots to a 47–7 blowout win through snow, sleet, and rain in the Patriots' last regular-season home game of 2008. Cassel, playing in snow for the first time ever, nevertheless completed 20 of 36 passes for 345 yards, three touchdowns, and no interceptions, while helping the Patriots remain in the hunt for the AFC East title. In a role reversal, Matt Leinart entered the game as the Cardinals' backup quarterback when Kurt Warner was pulled from the game with the Cardinals trailing 44–0; Leinart completed 6 of 14 passes, for 138 yards, a touchdown, and an interception.
