Purpose: Removable complete dentures function in an environment colonized by numerous microorganisms which attach to hard, non-shedding surfaces leading to various diseases, such as Denture-related stomatitis. The purpose of the study was to evaluate the combined effect of different polishing protocols and different denture cleansers on the surface roughness of 3 heat-polymerized polymethyl methacrylate (PMMA) denture base materials. Materials and Methods: The 216 specimens were fabricated from 3 commercially available heat-polymerized denture base acrylic resins. Specimens of each resin were divided in 3 groups, each receiving one of 3 different surface treatments (laboratory, chairside, and carbide bur). Specimens of each group were further divided into 3 sub-groups which were immersed in either distilled water or each of the tested denture cleansers for 15 minutes. A year’s cycle of cleansers use was simulated. Surface roughness was measured using an optical profilometer. Results: Statistical analysis of the data revealed that surface roughness was influenced by the type of acrylic resin, the polishing method employed but not by the immersion in denture cleansers. There was a statistically significant interaction between levels of immersion solution and material and a significant two-way interaction between level of surface polishing and material. Conclusion: Within the limitations of this study, it was concluded that immersion in the tested denture cleansers did not alter on average the surface roughness values of the tested materials, irrespective of the polishing procedure, after a simulated period of 365 days. Thus, they can be safely used as a method of removable denture hygiene.