This study was conducted on twenty one patients from the outpatient's clinic in the faculty of oral and dental medicine Cairo University. The current study was carried out on patients wearing complete dentures lined with soft resilient liner to evaluate the effectiveness of three different microwave watts and exposure times on disinfection and dimensional changes of the complete dentures. The patients were divided into three groups, each group have seven patients. In the first group, the disinfectant was 350 watt for five minutes. In second group, it was 500 watt for three minutes and in the third group, the disinfectant was 650 watt for two minutes. The effectiveness of the three disinfectants was evaluated by taking four swabs from the maxillary denture and five swabs from the mucosa of the palate. The swabs were taken before disinfectant application, immediately after denture final adjustment, after one week, after two weeks and after three weeks of denture insertion and a measurement of the dimensional changes before and after every steps. The results were as follows: Dimensional changes of the denture base before and after disinfection by three different microwave watts were not observed. The number of adhering microorganism on denture lined with soft resilient liner was more than number of adhering microorganism to the mucosa. The three different watts used for denture disinfection were effective in decreasing the number of microorganism in both mucosal swabs and denture swabs: as following: a) The 650 watt was superior as disinfection when compared the other two watt. It was followed by 500 watt. The least effective was the 350 watt (i.e increase the watt lead to decreasing microorganism) (all significant). b) In mucosa swabs the decrease was non-significant. The adhesion of microorganisms increase by time on mucosa and a denture base.