OBJECTIVE: To confirm the efficacy of rizatriptan 10 mg orally disintegrating tablet (ODT) for the elimination of migraine-associated nausea. BACKGROUND: Pooled studies of rizatriptan analyzing elimination of nausea as a secondary endpoint showed that 65% of rizatriptan patients reported elimination of nausea at 2 hours compared with 41% of patients taking placebo. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled single-attack trial enrolling adult patients with at least a 6-month history of migraine who typically experience migraine-associated nausea. Patients treated a moderate or severe migraine headache at the earliest sign of nausea with either rizatriptan 10 mg ODT or placebo (2 : 1). The primary endpoint was elimination of nausea at 2 hours postdose, and the secondary endpoint was pain relief at 2 hours postdose. RESULTS: Although not statistically significant, a greater percentage of patients had elimination of nausea at 2 hours with rizatriptan compared with placebo (70.3% vs 62.0%, P = .165, odds ratio [95% CI] = 1.45 [0.86, 2.46]). When patients were grouped by baseline headache severity, rizatriptan showed a greater advantage than placebo for patients with moderate pain (rizatriptan 72.8% vs placebo 57.4%), but no difference for patients with severe pain (rizatriptan 67.7% vs placebo 66.7%). There were significantly more patients who achieved 2-hour pain relief with rizatriptan (69.7% vs 54.3%, P = .012, odds ratio [95% CI] = 1.94 [1.16, 3.25]). CONCLUSION: Although the efficacy of rizatriptan 10 mg ODT for the elimination of migraine-associated nausea was comparable to that seen in previous rizatriptan trials, the higher-than-usual placebo response prevented a finding of a statistically significant difference. There was a sizable difference in placebo response between patients who treated moderate vs severe migraine. Rizatriptan was effective for 2-hour pain relief.