OBJECTIVES: A decision-analysis model parameterised for Scotland was used to evaluate the cost-effectiveness of intranasal fentanyl spray (INFS, Instanyl®) compared with oral transmucosal fentanyl citrate lozenge (OTFC, Actiq®) and oral transmucosal fentanyl buccal tablet (FBT, Effentora®) for the treatment of BTCP. METHODS: The model estimated costs and benefits associated with INFS, OTFC and FBT. Relative analgesic efficacy of the interventions was derived from a meta-analysis of six randomised controlled trials. The percentage of BTCP avoided was estimated from the pain intensity (PI) course of a BTCP episode with and without treatment. Resource use and quality of life gains were estimated based on reductions in PI. The relationship between PI and utility was derived from a time-trade off study in the UK general population. Resource use and unit cost data were obtained from the literature and validated by clinical experts. Uncertainty in the source data was incorporated by means of one-way sensitivity analyses, probabilistic sensitivity analyses and different scenario analyses. RESULTS: For the base-case scenario, 3 BTCP episodes/day, a background PI of 2, a time-horizon of 365 days and equal prices for INFS and OTFC irrespective of dosage were assumed. With INFS, 55% of BTCP (95% Uncertainty Interval: 45–66%) was avoided, greater than expected with OTFC (29%; 21–39%) or FBT (31%; 25–39%). INFS was dominant versus OTFC and cost-effective versus FBT. Despite the uncertainty in the source data, there is a >99% probability that INFS is the most cost-effective intervention. Sensitivity and scenario analyses did not change the main conclusion. CONCLUSIONS: Greater efficacy of INFS in pain reduction is expected to reduce medical resource use and result in cost-savings for healthcare providers and quality of life gains for patients. INFS is a cost-effective treatment for BTCP compared with OTFC and FBT in Scotland.