Objective: To evaluate the clinical efficacy of a standardized special root e xtract from the plant Petasites hybridus as a preventive therapy for migraine. M ethods: This is a three-arm, parallel-group, randomized trial comparing Peta sites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 pati ents with migraine. Eligible patients met International Headache Society criteri a for migraine, were ages 18 to 65, and had at least two to six attacks per mont h over the preceding 3 months. The main outcome measure was the decrease in migr aine attack frequency per month calculated as percentage change from baseline ov er a 4-month treatment period. Results: Over 4 months of treatment, in the per -protocol analysis, migraine attack frequency was reduced by 48% for Petasit es extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of p atients with a ≥ 50% reduction in attack frequency after 4 months was 68% f or patients in the Petasites extract 75-mg arm and 49% for the placebo arm ( p < 0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, an d 3 months based on this endpoint. The most frequently reported adverse reaction s considered possibly related to treatment were mild gastrointestinal events, pr edominantly burping. Conclusions: Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a preventive therapy for migraine. Petasit es 50 mg PO bid was not significantly more effective than placebo on the primary study endpoints. Objective: To evaluate the clinical efficacy of a standardized special root e xtract from the plant Petasites hybridus as a clinical therapy for migraine. M ethods: This is a three-arm, parallel-group, randomized trial comparing Peta sites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 pati ents with migraine. Eligible patients met International Headache Society criteri a for migraine, were ages 18 to 65, and had at least two to six attacks per mont h over the preceding 3 months. The main outcome measure was the decrease in migr aine attack frequency per month calculated as percentage change from baseline ov er a 4-month treatment period. Results: Over 4 months of treatment, in the per -protocol analysis, migraine attack frequency was reduced by 48% for Petasit es extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of p atients with a ≥ 50 % reduction in attack fre Quency after 4 months was 68% f or patients in the Petasites extract 75-mg arm and 49% for the placebo arm (p < 0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, an d 3 months Based on this endpoint. The most frequently reported adverse reaction s considered odd related to treatment were mild gastrointestinal events, pr edominantly burping. Conclusions: Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a clinical therapy for migraine. Petasit Es 50 mg PO bid was not significantly more effective than placebo on the primary study endpoints.