Ten years after the first American Pie movie, three new hapless virgins discover the Bible hidden in the school library at East Great Falls High. Unfortunately for them, the book is ruined, and with incomplete advice, the Bible leads them on a hilarious journey to lose their virginity.
| Actor | Role |
|---|---|
 Bug HallRob | Rob |
 Brandon HardestyLube | Lube |
 Kevin M. HortonNathan | Nathan |
 Beth BehrsHeidi | Heidi |
 Melanie PapaliaDana | Dana |
 Jennifer HollandAshley | Ashley |
 John Patrick JordanStifler | Stifler |
 Louisa LyttonImogen | Imogen |
 Sherman HemsleyPastor | Pastor |
 Eugene LevyMr. Levenstein | Mr. Levenstein |
 Curtis ArmstrongMr. O'Donnell | Mr. O'Donnell |
 Jim WynorskiEddie | Eddie |
 Rosanna ArquetteRob's Mom | Rob's Mom |
 Dustin DiamondAlumnus Guy #1 | Alumnus Guy #1 |
 Kevin FederlineCanadian Border Guard | Canadian Border Guard |
 C. Thomas HowellAlumnus Guy #2 | Alumnus Guy #2 |
 Christopher KnightAlumnus Guy #3 | Alumnus Guy #3 |
 Tim MathesonAlumnus Guy #4 | Alumnus Guy #4 |
 Bret MichaelsSelf | Self |
 Steve RailsbackAlumnus Guy #5 | Alumnus Guy #5 |
 Robert RomanusAlumnus Guy #6 | Alumnus Guy #6 |
 Cindy BusbyAmy | Amy |
 Naomi HewerAlyson | Alyson |
 Edwin PerezGibbs | Gibbs |
 Nico McEownCody | Cody |
 Karin KonovalStore Manager | Store Manager |
 Carrie KeaganSales Lady | Sales Lady |
| WWilla PotterKrissi with an 'I' | Krissi with an 'I' |
| MMeghan FeenstraSarah | Sarah |
 Jasmine MooneyJackie | Jackie |