OBJECTIVE: Breakthrough cancer pain (BTCP) represents a considerable economic burden. A decision-analysis model was developed to evaluate the cost-effectiveness of intranasal fentanyl spray (INFS) compared with oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT) for the treatment of BTCP. METHODS: The model was parameterized for Sweden to estimate the costs and benefits associated with treatments. Expected reductions in pain intensity (PI; measured on a numeric rating scale ranging from 0 to 10) per BTCP episodes were translated into resource use and quality-adjusted life years (QALYs). Relative analgesic efficacy of interventions was derived from a mixed treatment comparison of six randomized controlled trials. The relationship between PI and utility was obtained from a time-trade off study in the general population. Resource use and unit cost data were obtained from the literature and validated by Swedish clinical experts. The base case scenario assumed three BTCP episodes/day, a background PI of 2, and a time horizon of 180 days. Prices of INFS and OTFC were assumed to be equal with FBT ∼14% less. Uncertainty in the source data was incorporated by probabilistic sensitivity analyses and different scenario analyses. RESULTS: With INFS, 55% of BTCP (95% uncertainty interval [UI]: 46-68%) was avoided, which is greater than expected with OTFC (29%; UI 22-38%) or FBT (31%; UI 25-39%). INFS was dominating OTFC (resulting in 0.046 QALY gain and saving 174 Euros with a time horizon of 180 days) and cost-effective versus FBT (incremental cost-effectiveness ratio 12203 Euros/QALY). Despite uncertainty in the source data, there is a >99% probability that INFS is the most cost-effective intervention. CONCLUSION: Given inherent limitations of modelling studies, the greater efficacy of INFS translates to cost and QALY advantages over competing interventions in the treatment for BTCP in Sweden.