Current migraine preventive therapies are often unsatisfactory because of their limited efficacy, adverse effects, and drug interactions. An open-label, noncontrolled study of botulinum toxin type A (BTX-A) suggested some benefits for patients with migraine. To assess the efficacy and safety of BTX-A, a randomized, double-blind, vehicle-controlled, parallel group study was conducted in 32 patients with a history of 2 to 8 migraine attacks per month, with or without aura. The patients were randomized to receive single administrations of 50-U BTX-A or vehicle injected into multiple sites of pericranial muscles at the same visit. Patients kept daily diaries in which they recorded outcome measures like migraine frequency, migraine severity, and the occurrence of migraine-associated symptoms. Patients graded symptoms on a 4-point scale ranging from grades 0 to 3 before and up to 3-months after treatment. The assessments were made at 0, 1, and 3 months. The primary efficacy parameters included number of headaches resolved (grade 3/2 to grade 0) and alleviation of other accompanying symptoms of migraine. The supplementary end point included improvement in quality of life (QOL). About 75% of patients reported complete relief to mild headache (grade 0–1) by BTX-A and none by placebo group. Patient' QOL parameters like energy/vitality and feelings and concerns about the treatment had shown considerable improvement. However, normal day-to-day work functioning and social interactions deteriorated. No adverse effects were reported in any of the patients in either of the groups during the study. It is evident from the study that pericranial injection of 50-U BTX-A showed good efficacy and tolerability as a prophylactic agent. However, this therapy will be expensive to the patients, but it is far superior in providing relief to the patients compared with existing therapies.