Purpose: This study evaluated the influence of fatigue loading on the performance of an adhesive and a nonadhesive cement for cast post-and-core restorations in maxillary premolars. Materials and Methods: The adhesive cement used was Panavia 21, a resin-based composite cement, and the nonadhesive cement was PhosphaCem/C, a zinc-oxy-phosphate cement. The coronal sections of single-rooted human maxillary premolars were removed at the level of the proximal CEJ. After endodontic treatment, a cast post and core was prepared for each tooth and cemented into the root canal with either Panavia 21 (n = 8) or PhosphaCem/C (n = 8). Half of the specimens from each cement group were exposed to fatigue loading almost perpendicular to the axial axis; the other half were used as controls. Three parallel transverse root sections were cut from each specimen and used for evaluation of the influence of fatigue loading. For each section, cement integrity was studied by SEM, and retention strength of the cemented post section was determined with a push-out test. Results: For SEM evaluation and the push-out test, Panavia 21 proved significantly better than PhosphaCem/C. However, fatigue loading did not show any effect. Conclusion: Under the conditions of this study, fatiguing of cemented cast post-and-core restorations was not decisive as a single test to evaluate the quality of the cement.