Aims: This in vitro study was conducted to evaluate and compare the antimicrobial efficacy of various disinfectants on different denture base materials. Settings and Design: Invitro analytical study Methods and Material: 64 specimens of PMMA, Polyamide, Cobalt chromium and PEEK were fabricated (n=16). Three denture cleansers were evaluated i.e sodium perborate, thyme oil and ozonated water. Distilled water served as control group. The contamination of specimens was done by Candida albicans. The contaminated specimens were disinfected by denture cleansers and cultured for candida albicans using Hi Chrome culture media. The colonies of candida albicans grown on Hi Chrome agar were counted. Data was tabulated and subjected to statistical analysis. Statistical analysis used: Two-way analysis of variance (ANOVA) of mean values was performed followed by Tukey’s HSD and ‘t’ test for Post hoc analysis for pair wise comparison. The level of significance was set at p≤0.05. Results: Among the denture base materials, PEEK exhibited least number of colonies of candida albicans, followed by cobalt chromium, polyamide and PMMA. Among the various denture cleansers, sodium perborate exhibited least number of colonies of candida albicans followed by ozonated water, thyme oil and distilled water. Sodium perborate and ozonated water found to be equally effective in reducing number of candida albicans colonies (statistically non-significant). Thyme oil reduced the number of colonies of candida albicans on cobalt chromium and PEEK while it was not effective on PMMA and polyamide. Conclusions: Among the denture cleansers, sodium perborate and ozonated water found to be equally effective in reducing number of candida albicans colonies in all denture base materials. Thyme oil reduced the number of colonies on cobalt chromium and PEEK while it was less effective on PMMA and polyamide. Choice of denture cleansers must be based on type of materials, mode of action of denture cleansers and interaction of denture cleansers and denture base materials between them.