OBJECTIVES: The objective of this study was to compare the cost-effectiveness of eletriptan to zolmitriptan using 24-hour sustained headache pain response as the measure of migraine treatment outcome. METHODS: This economic analysis was based on data derived from a randomized, multi-center, double-blind, double-dummy, parallel group, placebo controlled, single-attack study of treatment for acute migraine. Patients enrolled in the clinical trial were randomized to eletriptan 40mg, zolmitriptan 2.5mg, or placebo. The clinical efficacy data from the two active treatment arms were combined with published drug cost data to assess the relative cost-effectiveness of eletriptan versus zolmitriptan. The cost per successfully treated patient (CPSTP) was calculated for both treatment groups as the ratio of the total triptan cost for treating all patients to the number of patients classified as being successfully treated. The health authority costs included eletriptan 40mg at 3.40€ per dose and zolmitriptan 2.5mg at 3.58€ per dose. The 24-hour sustained headache pain response rate was the effectiveness measure used in the denominator of the CPSTP ratio. RESULTS: For the 24-hour sustained headache pain response measure, a significantly larger proportion of patients were successfully treated with eletriptan versus zolmitriptan (p=0.0099). The CPSTP estimates were 10.34€ (95% CI: 8.97€ – 12.17€) for eletriptan and 14.65€ (95% CI: 12.53€ – 17.45€) for zolmitriptan. CONCLUSIONS: For the 24-hour sustained headache response endpoint, eletriptan 40mg performed significantly better than zolmitriptan 2.5mg. For the cost per successfully treated patient, eletriptan costs were significantly lower compared to zolmitriptan costs. The results of this study add to the body of clinical and economic evidence supporting the use of eletriptan for the treatment of acute migraine, and can be used to assist decision makers in the allocation of scarce resources.