Purpose: This study was done to compare the microbial colonization of flexible thermoplastic nylon (bre.flex) and heat cured acrylic resin in obturators restoring acquired maxillary defects. Methods: The experiment was carried out on six patients with acquired maxillary defect who are in need of definitive obturator. Selected patients received metal framework prosthesis with heat cured acrylic resin bulb extending into the surgical site. At time of insertion a swab was obtained from the patients which represents the base line for situation I. Patients were followed after two and four weeks from wearing the obturator for microbiological evaluation and a swab was taken each time from the same place. In situation II, heat cured acrylic resin was replaced with flexible thermoplastic nylon (bre.flex) and a swab was obtained on the day of insertion as a base line for situation II. Patients were followed after two and four weeks from insertion of the replaced obturator for microbiological evaluation and a swab was taken each time from the same place. Swabs were obtained from the nasal surface of the surgical defect and immediately cultivated into three different media Blood Agar, Sabouraud Dextrose Agar and Macconkey media and incubated for microbiological evaluation. The identification and quantification of the isolated microorganisms were performed using conventional microbiological cultivation method. Finally, the collected data was tabulated and statistically analyzed. Results: The results obtained from this study revealed that, both conventional heat cured acrylic obturator and flexible thermoplastic nylon (bre.flex) obturator has the affinity to support microbial growth. However, the thermoplastic nylon (bre.flex) has lease affinity to microbial colonization than conventional heat cured acrylic obturator. Conclusion: Within the limitation of the present study, it is preferable to use flexible thermoplastic nylon (bre.flex) obturator for acquired maxillary defect patients than conventional heat cured acrylic obturator to reduce microbial growth and colonization.