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Purpose Severe radiation dermatitis (RD) is distressing and may have adverse long-term effects including fibrosis and telangiectasia. Treatment interruptions due to severe RD may increase the risk of recurrence. Two randomized trials of Mepitel film demonstrated efficacy in preventing severe RD in breast cancer, but this product has not been widely adopted in North America. We aimed to assess the feasibility and efficacy of Mepitel film for prevention of breast RD at a Canadian center. Methods and Materials Patients were stratified based on breast size and receipt of postmastectomy radiation therapy. The primary outcome was RD grade using the Common Terminology Criteria for Adverse Events. Secondary outcomes included moist desquamation, patient- and clinician-reported symptoms of skin toxicity, and cosmetic outcomes. Results Thirty patients receiving external beam radiation therapy to the breast or chest wall were enrolled. Two patients (6.7%) discontinued use of the Mepitel film before completing radiation therapy. No patients developed grade 3 RD or higher. Five patients (17.9%) developed grade 2 RD: 3 (10.7%) had moist desquamation, and 2 (7.1%) had brisk erythema without moist desquamation. Conclusions Mepitel film completely prevented grade 3 RD. Rates of moist desquamation and grade 2 RD were lower with Mepitel film than in studies using aqueous cream, but unlike previous trials of Mepitel film we did not achieve complete prevention of moist desquamation. Further research is needed to confirm the efficacy of Mepitel film versus standard prophylaxis for RD and identify the patients who will benefit the most from the film.