OBJECTIVE: To assess, via Monte Carlo simulation, the per-attack drug acquisition cost and effectiveness (proportion of patients pain-free two hours post-dose) of five oral triptan strategies for treatment of acute migraine headaches. METHODS: A Monte Carlo simulation model was used to estimate the average number of patients needed to treat (NNT), relative to placebo, to achieve the efficacy endpoint of one pain-free two hours post-dose (pain-free patient). Efficacy data was obtained from a published meta-analysis of 53 triptan-specific clinical trials. A normal distribution for the proportion of pain-free patients was used and was based on the means and 95% confidence intervals reported in the meta-analysis. Single-dose acquisition costs, based on average wholesale prices (2002US$), were applied to the NNT results, allowing for a per-attack assessment of the cost per pain-free patient. Oral triptans almotriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan were assessed in the simulation. RESULTS: After 10,000 iterations, the mean NNT (95%CI) to achieve one pain-free patient was 3.31 (2.97-3.71) for rizatriptan, 4.16 (2.83-6.54) for zolmitriptan, 5.06 (3.32-8.53) for almotriptan, 5.14 (4.50-5.92) for sumatriptan and 7.26 (5.52-9.96) for naratriptan. The mean cost (95%CI) per pain-free patient was $55.61 ($36.50-$93.70), $56.60 ($50.81-$63.44), $75.34 ($51.34-$118.61), $88.27 ($77.28-$101.70) and $145.27 ($110.38-$199.27) for almotriptan, rizatriptan, zolmitriptan, sumatriptan and naratriptan, respectively. Cost differences between almotriptan and rizatriptan were relatively small, with 38 percent of simulations resulting in cost savings per pain-free patient favoring rizatriptan. CONCLUSIONS: Inasmuch as the results suggested that almotriptan and rizatriptan may be similar on a cost per pain-free patient basis, the NNT results favored rizatriptan, with approximately two fewer patients needed to treat to achieve one pain-free patient. Future economic assessments, including endpoints such as tablet consumption per attack and consistency across multiple attacks, may provide further guidance as to the most cost-effective triptan strategies.