Purpose: To evaluate the marginal adaptation and fracture load of composite resin onlays reinforced with different substructures. Materials and Methods: Thirty-two extracted, caries-free premolars were selected for this study and endodontically treated. Group 1 was used as the control group, and the teeth were restored only with as-manufactured composite resin overlays. Group 2 teeth were restored with composite resin overlays with 3 fiber-reinforced composite (FRC) layers placed horizontally on the bottom of the restoration. Group 3 teeth were restored with composite resin overlays with 6 fiber-reinforced composite (FRC) layers placed as in group 2. Group 4 teeth were restored with composite resin overlays and FRC placed with an anatomical design. All specimens underwent SEM evaluation of their marginal adaptation before and after thermocycling and cyclic mechanical loading. All specimens were then subjected to a fracture test, recording the value for the initial (IF) and final (FF) failure. Differences in the means were compared using matched-pairs t-tests and one-way ANOVA. The level of significance was set at α = 0.05. Results: No statistically significant difference between the four groups in terms of marginal adaptation was observed at the tooth/luting composite and luting composite/overlay interfaces before and after loading. The fracture loads of IF and FF, from most to least resistant were: group 4 (1431.8 ± 294.3 N / 1710.1 ± 326.6 N), group 3 (1428.1 ± 251.4 N / 1467.9 ± 242.4 N), group 2 (852.6 ± 413.5 N / 1058.1 ± 251.5 N) and group 1 (899.8 ± 352.7 N / 923.5 ± 318.8 N). Significant differences (p = 0.026) were observed comparing group 1 to groups 2 and 3, and group 1 to 4. Three irreparable fractures were found in group 3, four in group 2, and five in groups 1 and 4. Conclusions: The presence or absence of reinforcement and the different configuration of the reinforcement fibers affect fracture strength but only partially the failure modality. The presence or absence of reinforcement does not alter marginal adaptation. Keywords: FRC, endodontically treated teeth, glass fibers, fracture, marginal adaptation, onlays