Objective: The aim of this study was to evaluate and compare the effect of silicon based soft relining material "Multisil-Soft" and the acrylic based soft relining material "COE-SOF TM " accumulation oral floral in lateral maxillary defect. Materials and Methods: Type of study: Randomized clinical Trial (RCT) fourteen patients with lateral maxillectomy defect were taken the outpatient clinic, Oral and maxillofacial Prosthodontic department Faculty of Dentistry, Ain Shams university.Grouping: Patients were randomly divided into two equal groups. Group-I: Seven patients had received Definite obturator relined with silicon based soft relining material. Group-II: patients were rehabilitated with definite obturator relined with acrylic based soft relining material. microbiological samples were taken for bacterial count and bacterial DNA load detection by Polymerase chain reaction Real-time PCR. Microbial evaluation was performed at the time of relining, three and six months after relining of the obturator. Results:The results of this study revealed that the bacterial count was significantly greater for group II compared to group I at time of relining -3 months and at time of relining -6 months. On the other hand, the bacterial DNA load was significantly greater for group I compared to group II at the intervals at time of relining -3 months and at time of relining -6 months. Conclusion:Within the limitations of this study; it may be concluded that: Acrylic based relining material (COE-SOFTTM) is more heavily accumulation of oral floral than silicon based relining material (Multisil-Soft).