Objective: The purpose of this study was to evaluate the resistance of selected post-and-core systems to fatigue testing. Method and materials: A fatigue-testing machine and data acquisition software were developed for this in vitro test. Pulpless mandibular second premolars were treated with three different types of post-and-core system: (1) two different prefabricated posts with amalgam cores, (2) the same two pre-fabricated posts with resin composite cores, and (3) cast post and cores, which served as the control group. The fatigue-testing machine applied alternating buccal and lingual forces to the core until lateral movement of 0.0025 inches (63.5 um) was detected by a transducer contacting the surface of the core. This criterion represented initial cement failure. Results: Although groups using the resin composite core material exhibited a higher number of cycles prior to failure, there was no statistically significant difference between the different post-and-core systems. Conclusion: All of the post-and-core systems that were tested may be acceptable for restoring endodontically treated teeth.