Clinical trials of migraine therapy often require treatment when migraine pain intensity is moderate or severe, but many physicians find this practice artificial and patients often prefer to treat while pain is mild. This randomized, placebo-controlled study assessed the efficacy of zolmitriptan 2.5 mg in treating migraine while pain is mild, in patients who typically experience migraine attacks that are initially mild, but progress to moderate or severe. The intent-to-treat population comprised 280 patients (138 zolmitriptan; 148 placebo), with mean MIDAS grades of 29.6 (zolmitriptan) and 27.6 (placebo). Zolmitriptan 2.5 mg provided a significantly higher pain-free rate at 2 h (43.4% vs. 18.4% placebo; P < 0.0001). Significantly fewer zolmitriptan patients reported progression of headache pain to moderate or severe intensity 2 h postdose (53.7% vs. 70.4% placebo; P < 0.01), or required further medication within 24 h (46.4% vs. 71.1% placebo; P < 0.0001). The efficacy of zolmitriptan was more pronounced in patients treating during the first 15 min following pain onset. Adverse events were reported in 31.2% of patients treated with zolmitriptan (vs. 11.3% for placebo), and the incidence was lower in patients who treated early after attack onset. Zolmitriptan provides high efficacy when treating migraine while pain is mild, with the clinical benefits being more pronounced when treating early after migraine onset.