To characterize the biomechanical performance of fiber-reinforced composite 5-unit implant-supported fixed dental prostheses (FDPs) receiving individually milled crowns by insilico and fatigue analyses. Eighteen implant-supported five-unit fiber-reinforced composite frameworks with an individually prepared abutment design were fabricated, and ninety resin-matrix ceramic crowns were milled to fit each abutment. FDPs were subjected to step-stress accelerated-life testing with load delivered at the center of the pontic and at 2nd molar and 1st premolar until failure. The reliability of the prostheses combining all loaded data and of each loaded tooth was estimated for a mission of 50,000 cycles at 300, 600 and 900 N. Weibull parameters were calculated and plotted. Fractographic and finite element analysis were performed. Fatigue analysis demonstrated high probability of survival at 300 N, with no significant differences when the set load was increased to 600 and 900 N. 1st and 2nd molar dataset showed high reliability at 300 N, which remained high for the higher load missions; whereas 1st premolar dataset showed a significant decrease when the reliability at 300 N was compared to higher load missions. The characteristic-strength of the combined dataset was 1252 N, with 1st molar dataset presenting higher values relative to 2nd molar and 1st premolar, both significantly different. Failure modes comprised chiefly cohesive fracture within the crown material originated from cracks at the occlusal area, matching the maximum principal strain location. Five-unit implant-supported FDP with crowns individually cemented in a fiber-reinforced composite framework presented a high survival probability. Crown fracture comprised the main failure mode.