['Evaluate the influence of composite resin CAD-CAM restoration thickness on the in vitro fatigue resistance and failure mode of overlay-type restoration in endodontically treated premolars.', 'Thirty extracted premolars received root canal treatment followed by a standardized tooth preparation (1.5-, 2.5- or 3.5-mm cusp reduction, proximal gingival margins located 1.5mm below the CEJ, glass-ionomer base and immediately sealed dentin with Optibond FL). Restorations were milled using Cerec3 and FiltekMZ100 composite blocks. The intaglio surfaces of the overlays were sandblasted and silanated. Tooth preparations were sandblasted and etched before insertion of the restoration. All restorations were luted with Optibond FL and preheated FiltekZ100. A closed-loop servohydraulic unit was used for simulating cyclic isometric chewing at 5 Hz, starting with a load of 200 N (5000 cycles), followed by stages of 400, 600, 800, 1000, 1200 and 1400 N at a maximum of 30,000 cycles each. All samples were loaded until fracture or to a maximum of 185,000 cycles. Groups were compared using the Kaplan-Meier survival curves.', 'None of the restored premolars with the 1.5-mm cusp overlap restoration withstood all 185,000 loading cycles. With 2.5- and 3.5-mm cusp overlap, the survival rate was 30% and 40%, respectively. The rate of fracture below the CEJ was 60%, 60% and 30% for 1.5, 2.5 and 3.5 mm of cusp overlap, respectively. Survival of restored premolars with 2.5- and 3.5-mm cusp coverage was not significantly different (p=.23).'] Does thickness of CAD-CAM composite resin overlay influences fatigue resistance of endodontically treated premolars?