Introduction <p>While randomized clinical trials (RCT) confirmed superiority of Mepitel Film (MF) in reducing acute radiation dermatitis (ARD) compared to standard-of-care (SoC), the incremental cost difference has limited its use. A cost-effectiveness analysis (CEA) was conducted from a Canadian healthcare payer’s perspective to guide policy decisions.</p> Methods <p>A decision model was constructed to perform a CEA for MF compared to SoC (moisturizers) for prevention of grade 2 or higher ARD following adjuvant hypo-fractionated whole-breast radiotherapy (RT) based on a Canadian multicentre RCT. Direct and indirect cost data were collected from two oncology centers in Canada. Quality-of-life (QoL) utility values were derived from mapping Dermatology Life Quality Index (DLQI) scores for patients with grade 2 or higher ARD at week 6 of RT to EQ-5D. A willingness-to-pay (WTF) threshold of CAD 50,000 per quality-adjusted life years (QALY) gained was used. Deterministic and probabilistic sensitivity analyses were performed to address uncertainty in decision model assumptions.</p> Results <p>Base case analysis demonstrated that MF is cost-effective in preventing grade 2 or higher ARD as compared with SoC with an incremental cost-effectiveness ratio (ICER) of CAD 3366 per QALY gained. When indirect costs were included, MF resulted in an ICER of CAD 2823 per QALY gained. One-way sensitivity analysis showed that the results were most sensitive to the QoL utility value for ARD. Probabilistic sensitivity analysis confirmed that MF demonstrates 100% probability of cost-effectiveness at a $50,000 per QALY threshold.</p> Conclusions <p>MF is a cost-effective intervention for preventing high-grade ARD and should be recommended for patients with breast cancer undergoing adjuvant RT.</p>