OBJECTIVES: The objectives of this study were to compare the clinical efficacy and cost-effectiveness of eletriptan 40 mg vs. sumatriptan 100 mg for the acute treatment of migraine attack. METHODS: Data were extracted and pooled from three randomized head-to-head clinical trials comparing the efficacy of eletriptan 40 mg and sumatriptan 100 mg. Three composite measures of treatment success were used based on sustained response (no recurrence of moderate to severe headache or use of rescue medication from the stated time period to 24 hours post-dose): 1-hour sustained response, with improvement of headache pain from moderate to severe at baseline to mild or absent within 1 hour; 2-hour sustained response, with improvement to absent or mild pain within 2 hours post-dose; and 2-hour sustained pain-free, with improvement to pain-free within 2 hours. The cost per successfully treated patient (CPSTP) was calculated for each outcome based on the wholesale acquisition cost (WAC) for each medication (AnalySource(r), September 2003). The 95% confidence interval (CI) was calculated using bootstrapping technique. RESULTS: Eletriptan 40 mg was superior to sumatriptan 100 mg across each of the three outcomes: 1-hour sustained, 20% vs. 15% (P <0.01); 2-hour sustained, 41% vs. 34% (P <0.001); and 2-hour sustained pain-free, 22% vs. 15% (P <0.0001). The CPSTP was lower for eletriptan than sumatriptan for all three measures: 1-hour sustained response, $81 vs. $129; 2-hour sustained, $40 vs. $57; 2-hour sustained pain-free, $74 vs. $133. CONCLUSIONS: Eletriptan 40 mg had consistently greater positive clinical impact than sumatriptan 100 mg in the acute treatment of migraine. The greater efficacy and lower recurrence rate also translated into better cost-effectiveness.