Purpose: The purpose of this study was to evaluate the effectiveness of microwave irradiation on the disinfection of simulated complete dentures. Materials and Methods: Eighty dentures were fabricated in a standardized procedure and subjected to ethylene oxide sterilization. The dentures were individually inoculated (10⁷ cfu/mL) with tryptic soy broth (TSB) media containing one of the tested microorganisms (Candida albicans, Streptoccus aureus, Bacillus subtilis, and Pseudomonas aeruginosa). After 48 hours of incubation at 37oC, 40 dentures were individually immersed in 200 mL of water and submitted to microwave irradiation at 650 W for 6 minutes. Forty nonirradiated dentures were used as positive controls. Replicate aliquots (25 µL) of suspensions were plated at dilutions of 10-3 to 10-6 on plates of selective media appropriate for each organism. All plates were incubated at 37oC for 48 hours. TSB beakers with the microwaved dentures were incubated at 37oC for 7 more days. After incubation, the number of colony-forming units was counted and the data were statistically analyzed by Kruskal-Wallis test (α = .05). Results: No evidence of growth was observed at 48 hours for S aureus, B subtilis, and C albicans. Dentures contaminated with P aeruginosa showed small growth on 2 plates. After 7 days incubation at 37˚C, no growth was visible in the TSB beakers of S aureus and C albicans. Turbidity was observed in 3 broth beakers, 2 from P aeruginosa and 1 from B subtilis. Conclusion: Microwave irradiation for 6 minutes at 650 W produced sterilization of complete dentures contaminated with S aureus and C albicans and disinfection of those contaminated with P aeruginosa and B subtilis.