Purpose: The aim of this study was to evaluate the effect of occlusion and two different denture base material on muscle activity and masticatory efficiency of complete dentures. Material and Methods: Two complete dentures of different material, conventional and flexible denture base material with different occlusal schemes, starting with unbalanced occlusion and converted into bilateral balanced occlusion through three different ways of remounting, laboratory, clinical and intra-oral selective grinding applied on three different posterior teeth assemblies were delivered to patients who were totally edentulous (all were men range age 50-60 years). Muscle activity and masticatory efficiency were evaluated with two different type of food, carrots resembling hard food and banana resembling soft food. The occlusal schemes were switched on the patients' denture bases. Two-way repeated-measures ANOVA and t test were used to examine the alterations between the occlusal schemes, denture base materials and chewing strokes and their relations. Results: No significant difference was found in electromyographic activity or masticatory efficiency between the occlusal schemes and denture base materials with soft food (p<0.05). A significant difference was found in electromyographic activity and masticatory efficiency with bilateral balanced occlusion obtained through clinical remounting with flexible denture base material with hard food. Conclusions: Within the limitation of this study, it was concluded that complete dentures with bilateral balanced occlusion obtained through clinical remounting found significant differences in muscle activity and masticatory efficiency with hard food. Flexible dentures are better than conventional dentures in muscle activity and masticatory efficiency.