A validated migraine-specific questionnaire (24-h Migraine Quality of Life Questionnaire1: 24-h MQoLQ) was used to assess the impact of migraine and migraine therapy on health related quality of life during an acute migraine attack. Male and female migraineurs aged 18-55 years were randomized to placebo (n = 41), rizatriptan 2.5 mg (n = 47), 5 mg (n = 74), or 10 mg (n = 85) in a triple-blind, placebo-controlled clinical trial. Rizatriptan 5 mg and 10 mg were significantly more efficacious than placebo on pain relief and functional disability. After accounting, for multiple comparisons to placebo, rizatriptan 10 mg showed significantly better responses compared to placebo on three of five domains of 24-h MQoLQ (social functioning, migraine symptoms, and feelings/concerns). The O’Brien’s Rank Sum Test statistic showed a statistically significant overall difference on the 24-h MQoLQ between the 10 mg rizatriptan and placebo groups (p = 0.005) and for the overall close trend (p 0.001).