Background <p>Ceramic veneers are a common option for enhancing dental aesthetics by improving tooth form, shade, and function. Preparation design is considered a critical factor in the success of dental veneers, as it influences the failure load and fatigue survival of posterior minimally invasive ceramic veneer restorations. The purpose of the study is to compare the failure load and mode after fatigue among three types of veneer preparation designs for restoring premolars.</p> Methods <p>64 human premolars were equally divided into four groups. Group 1 had a buccal preparation depth of 0.7&#xa0;mm; Group 2 had an additional reduction of the buccal cusp; Group 3 had a mesio-occluso-distal box with dimensions of 2&#xa0;mm wide and 3&#xa0;mm deep. The remaining sound teeth served as the control group. Monolithic lithium disilicate restorations were cemented onto the prepared teeth with adhesive cement and then exposed to dynamic fatigue and thermocycling. Each specimen underwent a single load-to-failure test, and the discrepancy in failure load before and after fatigue was computed.</p> Results <p>No significant differences in initial failure load were observed among the four groups evaluated (<i>p &lt;</i>.075). A significant drop in failure load was observed in all groups after fatigue (P = 0.012). The failure loads of Groups I and II were significantly lower than those of Group III and the control (P &lt; 0.05).” Nevertheless, after fatigue, statistically significant differences were detected (<i>p &lt;</i>.013) as fatigue caused a substantial drop in failure load among all groups.</p> Conclusions <p>Within the limitations of this study, fatigue significantly reduced failure load in all groups. Veneer preparation design influenced post-fatigue strength, with more conservative designs showing better resistance. These findings underscore the impact of fatigue on structural integrity and the importance of tooth preparation design on fatigue resilience.</p>