Background: Hygiene and maintenance of removable prostheses are very important for the oral health. Elderly patients are not capable of this affair since they might have diseases in addition to being old; thus, they require new alternative methods. Objectives: The purpose of this study was to compare the disinfecting effects of three substances, water, normal saline and denture cleaning tablets Corega that patients commonly use as denture cleaning, against oral bacterial infections. Patients and Methods: In this study, complete maxillary dentures of 138 elderly individuals living in a nursing home (46 females and 92 males) with a mean age of 9 ± 75 years were studied. Their prostheses were soaked for 15 minutes randomly into one of the following substances: water, normal saline, or a solution containing denture cleaning tablets (Corega). Before and after this operation, samples were obtained by a third person using microbiological studies swabs. The samples were cultured and the colony forming units (CFU) were obtained. Data were evaluated by one-way ANOVA test. Results: Statistically, Corega reduced bacterial infections significantly more than water and normal saline (P = 0.0001). Water and normal saline had equal effects on reducing CFU. Conclusions: Denture cleaning tablet, Corega, is recommended for cleaning the prostheses, but using water or saline alone is not recommended.