Purpose To evaluate the fatigue failure load of distinct lithium disilicate restoration designs cemented on a chairside titanium base for maxillary anterior implant‐supported restorations. Materials and Methods A left‐maxillary incisor restoration was virtually designed and sorted into 3 groups: (n = 10/group; CTD: lithium disilicate crowns cemented on custom‐milled titanium abutments; VMLD: monolithic full‐contour lithium disilicate crowns cemented on a chairside titanium‐base; VCLD: lithium disilicate crowns bonded to lithium disilicate customized anatomic structures and then cemented onto a chairside titanium base). The chairside titanium base was air‐abraded with aluminum oxide particles. Subsequently, the titanium base was steam‐cleaned and air‐dried. Then a thin coat of a silane agent was applied. The intaglio surface of the ceramic components was treated with 5% hydrofluoric acid (HF) etching gel, followed by silanization, and bonded with a resin cement. The specimens were fatigued at 20 Hz, starting with a 100 N load (5000× load pulses), followed by stepwise loading from 400 N up to 1400 N (200 N increments) at a maximum of 30,000 cycles each. The failure loads, number of cycles, and fracture analysis were recorded. The data were statistically analyzed using one‐way ANOVA, followed by pairwise comparisons (p < 0.05). Kaplan‐Meier survival plots and Weibull survival analyses were reported. Results For catastrophic fatigue failure load and the total number of cycles for failure, VMLD (1260 N, 175,231 cycles) was significantly higher than VCLD (1080 N, 139,965 cycles) and CDT (1000 N, 133,185 cycles). VMLD had a higher Weibull modulus demonstrating greater structural reliability. Conclusion VMLD had the best fatigue failure resistance when compared with the other two groups.