This in vitro study aimed to find the best combination of mesostructure and veneering materials for full-arch implant-supported hybrid prostheses (HPs) in terms of the fracture resistance (FR) of their cantilevers.Three groups (n= 5 each) of maxillary HPs were fabricated: Group-1 (CC-A, control): Co-Cr frameworks coated with acrylic resin; Group-2 (CF-A): carbon fiber veneered with acrylic resin; and Group-3 (CF-R): carbon fiber coated with composite resin. All specimens were submitted to 5,000 thermal cycles (5 °C - 55 °C, dwell time: 30 s), and subjected to a single cantilever bending test in a universal testing machine (crosshead speed: 0.5 mm/min) until failure. The fracture pattern was assessed using stereo microscope and SEM. The one-way ANOVA and Bonferroni tests were run (α= 0.05).The FR yielded significant differences among the three groups (p< 0.001). CC-A samples reached the highest FR values (p≤ 0.001), whereas both CF-A and CF-R HPs exhibited the comparably (p= 0.107) lowest FR. CC-A specimens failed cohesively (100%): mostly without chipping (80%). CF-A mesostructures were always broken at the connections of the distal implants. CF-R prostheses often failed adhesively (80%).The HPs made of Co-Cr veneered with acrylic demonstrated the best mechanical behaviour, being the only group whose 13-mm long cantilevers exceeded the clinically acceptable FR of 900 N. The HPs constructed with carbon fiber frameworks showed, additionally, more unfavourable fracture patterns.For HPs with cantilevers up to 13 mm, Co-Cr mesostructures coated with acrylic may represent the optimum combination of materials.