Introduction: This study evaluated the risk of failure for an endodontically treated premolar with mesio occluso-distal palatal (MODP) preparation and 3 different computer-aided design/computer-aided manufacturing (CAD/CAM) ceramic restoration configurations. Methods: Three 3-dimensional finite element (FE) models designed with CAD/CAM ceramic onlay, endocrown, and conventional crown restorations were constructed to perform simulations. The Weibull function was incorporated with FE analysis to calculate the long-term failure probability relative to different load conditions. Results: The results indicated that the stress values on the enamel, dentin, and luting cement for endocrown restoration were the lowest values relative to the other 2 restorations. Weibull analysis revealed that the individual failure probability in the endocrown enamel, dentin, and luting cement obviously diminished more than those for onlay and conventional crown restorations. The overall failure probabilities were 27.5%, 1%, and 1% for onlay, endocrown, and conventional crown restorations, respectively, in normal occlusal condition. Conclusions: This numeric investigation suggests that endocrown and conventional crown restorations for endodontically treated premolars with MCDP preparation present similar longevity. (J Endod 2009;35:1391-1395)