Purpose: To compare the influence of surface roughness and accelerated aging on the mechanical properties of polymer-based and ceramic CAD/CAM materials. Materials and Methods: Three polymers (Lava Ultimate [LVU], VITA ENAMIC [ENA], and Shofu Block HC [SFB]) and one ceramic (IPS Empress CAD [EMP]) were selected for this study. The specimens were treated with the aim of measuring surface roughness (Ra [mm]) and its influence on the mechanical properties. The treatments were: polishing (POL); etching with 9.6% hydrofluoric acid for 90 seconds (ETC); airborne-particle abrasion with 50-μm aluminum oxide at 2-bar pressure (SBT); and airborne-particle abrasion with 50-μm aluminum oxide at 2-bar pressure plus etching with 9.6% hydrofluoric acid (SAC) for 90 seconds. Before and after the accelerated aging (AA) protocol (30,000 cycles, 5°C and 55°C), the specimens were subjected to the 3-point bending test. The data were analyzed with two-way and three-way ANOVA and post hoc Tukey test (P .05). Results: The surface roughness ranged from 0.24 μm to 1.96 μm, with statistically significant differences (P .05). The highest surface roughness, in descending order, was exhibited by: LVU > SFB > EMP > ENA. The AA demonstrated an influence on the flexural strength of LVU, ENA, and SFB. The surface treatment did not affect the flexural moduli of the materials tested. The LVU and SFB showed decreased moduli of resilience after the AA; however, modulus of resilience was not influenced by surface treatment. Conclusion: The polymer-based materials were affected by AA. In addition, surface treatment could jeopardize their mechanical properties in certain conditions.