Peripheral arterial disease (PAD) is a condition in which there is blockage or narrowing of the arteries that carry blood to the peripheries. The most common symptom of PAD is intermittent claudication (IC), characterised by pain in the legs on walking that is relieved with rest. Symptoms of IC can be managed with exercise therapy and/or vasoactive drugs. OBJECTIVES: To assess the cost-effectiveness of the vasoactive drugs cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for IC due to PAD in adults whose symptoms continue despite a period of conservative management. METHODS: A Markov decision model was developed to assess the lifetime costs and benefits of each vasoactive drug compared with no vasoactive drug and with each other. Regression analysis was undertaken to model the relationship between maximum walking distance and utility based on patient-level data from a trial of cilostazol to enable quality of life impacts to be estimated for the other drugs under consideration. Resource use data were sourced from the literature and a comprehensive sensitivity analysis was undertaken. RESULTS: The economic evaluation suggests that naftidrofuryl oxalate is more effective and less costly than cilostazol and pentoxifylline and has an estimated cost per QALY gained of around £6070 compared with no vasoactive drug. Whilst there is limited effectiveness evidence associated with inositol nicotinate, threshold analysis suggests that it is unlikely to be considered to be cost-effective due to its more expensive acquisition cost. CONCLUSIONS: This is the first published cost-utility analysis in this area which extrapolates data over a lifetime and uses effectiveness evidence from a network meta-analysis. In contrast to previous guidelines recommending cilostazol, this comprehensive analysis suggests that naftidrofuryl oxalate is the only vasoactive drug for PAD which is likely to be cost-effective at a willingness to pay threshold of £20,000 per QALY gained.