BACKGROUND: In the current literature, there is neither a reported systematic review comparing the efficacy of triptans at 30 minutes and 1 hour after the migraine treatment, nor data related to efficacy of new marketed triptans. OBJECTIVE: The main objective of this analysis was to compare the efficacy and tolerability of currently marketed oral, non-reencapsulated triptan formulations vs placebo in the treatment of moderate-to-severe migraine attacks. METHODS: A systematic review of double-blind, randomized clinical trials reporting data after a single migraine attack was conducted. Efficacy results are shown using relative risk ratios with 95% confidence intervals. A sensitivity analysis was also conducted. RESULTS: After reviewing 221 publications, 38 studies were included. All marketed triptans provided significant relief and/or absence of pain at 2 hours, and relief at 1 hour when compared with placebo. After 30 minutes, fast-dissolving sumatriptan 50 and 100 mg, sumatriptan 50 mg, and rizatriptan 10 mg showed significant relief when compared to placebo, whereas the fast-dissolving formulation of sumatriptan 100 mg was the only oral triptan that was superior to placebo in meeting the pain-free endpoint. On the other hand, fast-dissolving sumatriptan 50 and 100 mg and eletriptan 40 mg showed a lower rate of recurrence than placebo, whereas rizatriptan 10 mg was the only triptan with a recurrence rate greater than that of placebo. Adverse events associated with treatment with tablet formulations of sumatriptan and zolmitriptan were significantly more frequent than those of the placebo group. The inclusion of trials with reencapsulated triptans in the analysis introduced minor specific changes in these results. CONCLUSION: This analysis updates the comparative data available for the 7 currently marketed oral triptans and clearly demonstrates their efficacy when compared to placebo, even with stricter endpoints, such as efficacy at 30 minutes. No triptan exhibited better tolerability than placebo. Results are diverse, depending on the triptan, which probably is a reflection of heterogeneous pharmacokinetics.