Purpose: This study evaluated the marginal adaptation, fracture modes, and loads to failure of different mesio-occlusal- distal (MOD) restorations in root canal treated molars in vitro. Materials and Methods: Forty mandibular first molars were randomly assigned to five groups (n = 8): UTR= untreated, RCT-AM= root-canal treated (RCT)+amalgam filling; RCT-COM= RCT+direct composite resin restoration; RCTFRC= RCT+composite resin restoration with two layers of multidirectional woven glass fibers; RCT-CER= RCT+ceramic inlay. All teeth were subjected to thermocycling and mechanical loading (TCML) in a computer-controlled masticator (1,200,000 loads, 49 N, 1.7 Hz, 3000 temperature cycles of 5°C to 50°C). Marginal adaptation was evaluated before and after TCML by scanning electron microscopy at 200X at the tooth/restoration interfaces. After TCML, all specimens were loaded to failure in a universal testing machine at 0.5 mm/min. Failure types were analyzed and scored (reparable: modes 1 and 2; catastrophic: modes 3 to 5). Data were analyzed with ANOVA and Bonferroni correction. Results: Marginal adaptation decreased significantly after TCML in all groups. The highest decrease was observed in RCT-FRC (before: 89.9 ± 2.2%, after TCML: 49.8 ± 11.9%) and the lowest in RCT-CER (before TCML: 90.3 ± 2.6% after TCML 80.4 ± 9.0%). Loads to failure (in N) were in descending order as follows: UTR: 3048 ± 905; RCT-CER: 1853 ± 477; RCT-AM: 1447 ± 363; RCT-FRC: 1066 ± 306; RCT-COM 960 ± 228. While UTR resulted in statistically higher loads to failure than those of all other groups (p 0.0001), RCT-CER showed significantly higher results than those of RCT-COM (p = 0.0014) and RCT-FRC (p = 0.0042). The UTR group showed exclusively reparable failures in the form of either superficial (mode 1) or complete cusp chipping (mode 2), but all restored teeth exhibited catastrophic failures involving fractures along or through the restoration (modes 3 to 5). Conclusion: None of the restored teeth in any group were able to bear the same load level as the natural teeth. With regard to marginal adaptation and fracture resistance, luted ceramic inlays were advantageous. The integration of FRC in the restoration had no positive effect on the fracture resistance. FRC application showed a negative effect on marginal adaptation of composite resin restorations. Keywords: ceramic, fiber reinforced composite, fracture resistance, inlay, intracoronal restoration, marginal adaptation, root canal treated teeth