Purpose: The purpose of this research was to compare between the effect of denture base materials and their processing techniques on palatal denture base adaptation and candidal colonization. Materials and methods: Thirty identical denture bases was constructed by silicon mold which was made from a educational edentulous maxillary cast . Thirty maxillary stone casts were obtained by pouring hard dental stone in the previous silicon mold . Sheets of wax with 2mm thickness, each were adapted to their corresponding stone casts then divided equally into three groups. Group I: Ten maxillary heat cured acrylic resin denture bases processed by long cycle hot water bath curing technique. Group II: ten maxillary acrylic resin denture bases processed by microwave energy. Group III: Ten maxillary monomer free thermoplastic resin denture bases processed by sabelix injecting system. Palatal denture base adaptation and candidal colonization were evaluated. The data was recorded and statistically analyzed. Results: The results of this study showed that statistically there was significant difference in palatal denture base adaptation between the tested groups as(p=0.024). The least mean gap (stone thickness) at the posterior palatal seal area was found in Acrifast denture base resin (G III) followed by GI. The least mean numbers of candidal colonies for the three groups was found in Acrifast denture base resin (G III) followed by GI . Statistically there was highly significant difference of candidal colonization between the three tested groups as(p<0.001). Conclusion: Based on the limits of this study, it could be concluded that injectable monomer free thermoplastic resin denture base material is preferred to minimize candidal colonization, enhance the accuracy of denture base adaptation and increase the opportunity for obtaining successful complete denture