Background: Migraine headache are usually characterized by pain on one or both sides of the head1. Migraine headaches are often accompanied by photophobia, phonophobia and vomiting. Pharmacological treatment is traditionally divided into acute or symptomatic treatment, and preventive treatment or prophylaxis. Most studies have evaluated the efficacy of such drugs alone; however, there are some studies with propranolol and tricyclic agents in association with other drugs. The clinical experience with combination therapy for migraine seems to be a rational approach when monotherapy fails and when migraine is refractory. Several drugs are used individually for migraine prophylaxis. Objective: The purpose of the present study was to compare the propranolol and amitriptyline as monotherapy for the prophylaxis of migraine. Materials and methods: This is a prospective, double-blinded, randomized, comparative, with a parallel group design and single center study conducted at Department of General Medicine at Surabhi Institute of Medical Sciences. Patients between 18 and 70 years of age, of either sex (male/female) with a diagnosis of Migraine either with or without aura as per The International Classification of Headache Disorders (ICHD) criteria were recruited in the study. Patients had more than two attacks of headache per month, each episode lasting for more than 2 days > 2 episodes/months. Result: In both the groups, maximum number of patients were in the age group of 5-25 years and least number of patients were 46-65 years of age. Mean age in group 1 patients were 29.25±9.75 and in Group 2 patients were 30.05±9.71. There was no statistically significant difference in mean age of patient from Group 1 and Group 2 patients with unpaired t test. the mean severity of Attack of migraine in Group 1 at period 1 was 4.95 with SD of 1.88 and period 2 was 4.15 with SD 1.68. In Group 2 during period 1 was 4.05 with SD of 1.75 and in period 2 mean 4.81 with SD 1.85. These was statistically significant difference in Group 1 and Group 2 (p=0.028) with Unpaired t test. Conclusion: Migraine is one of the most common disabling conditions in the world, which undermines quality of life; the mean number of migraine attacks in the Amitriptyline and the Propranolol group decreased as the duration of treatment increased