Purpose: This study assessed the influence of palatal cuspal coverage on the in vitro fatigue resistance and failure mode of Class II resin composite restorations including replacement of the buccal cusp in premolars. Materials and Methods: A master model was made of a maxillary premolar with an MOD amalgam cavity and a simulated fracture of the buccal cusp from the isthmus floor to the CEJ. Using a copymilling machine, this preparation was copied to 20 extracted human maxillary premolars (group A). Subsequently, the palatal cusp was reduced by 1.5 mm; this modified preparation was copied to 20 additional maxillary premolars (group B). Direct resin composite restorations were made in all teeth. Cyclic load (5 Hz) was applied, starting with a load of 200 N (10,000 cycles), followed by stages of 400, 600, 800, and 1,000 N at a maximum of 50,000 cycles each. Samples were loaded until fracture or to a maximum of 210,000 cycles. Results: Of the restored premolars of group A, 20% withstood all 210,000 loading cycles; in group B, this figure was 55%. In group A, 19% of the fractures ended below the CEJ; in group B, 78% did. Conclusion: Palatal cuspal coverage increased the fatigue resistance of Class II resin composite restorations with replacement of the buccal cusp in premolars. However, fractures of restorations with cuspal coverage led to more dramatic failures that made restoration virtually impossible. This suggests caution in lowering remaining cusps for these adhesive restorations in the clinical situation.