Sumatriptan, notably after subcutaneous administration, is highly effective in the acute treatment of migraine in the majority of patients. The response is consistent within patients and over time. To determine risk factors for nonresponse to sumatriptan, we compared clinical characteristics. In responders and nonresponders and, within patients, between attacks with and without response. We found no differences at the strict level of significance (P<0.001 because of multiple comparisons), but only tendencies for differences (0.001<P<.0.05) in either the subcutaneous or oral groups. In the subcutaneous group, nonresponders had a higher body mass index, migraine onset at an earlier age, and, most importantly, they treated their migraine attacks earlier. In the oral group, nonresponders had attacks associated with more severe vomiting and photophobia, more often went to sleep or rest, and more frequently experienced initial worsening of the headache after sumatriptan administration. Within patients, no differences were found between attacks with and without response. In conclusion, we found few, If any, clinically relevant risk factors for nonresponse to sumatriptan. Administration of sumatriptan too early was the strongest indicator and should be avoided.