The present investigation hypothesized that the reliability of reduced-thickness monolithic lithium disilicate crowns is high relative to that of veneered zirconia (Y-TZP) and comparable with that of metal ceramic (MCR) systems. CAD/CAM first mandibular molar full-crown preparations were produced with uniform thicknesses of either 1.0-mm or 2.0-mm occlusal and axial reduction, then replicated in composite for standard crown dies. Monolithic 1.0-mm (MON) and 2.0-mm CAD/CAM lithium disilicate crowns, the latter with a buccal thin veneer (BTV) of 0.5 mm, were fabricated and then sliding-contact-fatigued (step-stress method) until failure or suspension (n = 18/group). Crack evolution was followed, and fractography of post mortem specimens was performed and compared with that of clinical specimens. Use level probability Weibull calculation (use load = 1,200 N) showed interval overlaps between MON and BTV. There was no significant difference between the Weibull characteristic failure loads of MON and BTV (1,535 N [90% CI 1,354-1,740] and 1,609 N [90% CI 1,512-1,712], respectively), which were significantly higher than that of Y-TZP (370 N [90% CI 322-427]) and comparable with that of MCR (1,304 N [90% CI 1,203-1,414]), validating the study hypothesis.