Computer-aided design/computer-aided manufacturing (CAD/CAM) materials were submitted to thermocycling, to identify changes in mechanical behavior. Four CAD/CAM materials were divided in four subordinate groups (n=9): (1) dry out for 7 days, (2) distilled water at 37oC for 7 days, (3) 60,000 thermocycles, and (4) 120,000 thermocycles. Following thermocycling, samples were submitted to three-point bending test. Two-way ANOVA and post-hoc Tukey's test were performed (α=0.05). The IPS e.max CAD had a flexural strength of 396±75 MPa and flexural modulus of 84±11 GPa, followed by Vita Enamic with values of 153±17 MPa and 28±5 GPa respectively. The flexural strength recorded for Lava Ultimate was 149±28 MPa and the flexural modulus was 12±3 GPa. Vitablocs Mark II had the lowest flexural strength values (125±10 MPa) and a flexural modulus of 49±15 GPa. Although polymer-based materials have similar mechanical properties compared to ceramics, they are affected by thermo cycling conditions.