Background:Migraine is a primary neurovascular headache disorder characterize by moderate to severe headaches, most often unilateral and generally associated with nausea and increased sensitivity to light and sound. Several factors can trigger migraine are probable contributing factors while others are possible or unproven such as:stress, hormonal changes, skipped meal, smoking, odour etc.Propranolol (non selective beta blocker) is the most common and one of the most effective first line medication used for migraine prophylaxis. Flunarizine (Calcium channel blocker) is acknowledged in numerous countries and included in numerous national guidelines for prophylaxis of migraine.We therefore intended to carry out this study and produce more data to support the choice of a medication for migraine prophylaxis that is both more effective and has a better safety profile.Aim: The aim of our study was to compare safety and efficacy of propranolol with flunarizine in adult patients suffering from migraine as prophylactic drugs. Objectives: 1) To evaluate safety and efficacy of propranolol.2) To evaluate safety and efficacy of flunarizine. Material and Methods: This comparative, prospective, randomized, and academic interventional study was conducted in tertiary care hospital of North India. A total of 76 patients satisfying the eligibility criteria were randomized into 2 groups to receive either the Tablet Propranolol 40 mg per day for first 5 days then 40 mg twice a day for 2 months or Tablet Flunarizine 10 mg per day for 2 months. A general evaluation, physical examination and routine investigations were performed on the first visit and repeated after every one month of treatment for next 2 months. Patient also assessed with VAS (Visual Analogue Scale) for headache intensity 1 (mild) to 10 (excruciating), to check extent of a patient’s disease. Results:Group A (89.2%) and Group B (52.8%) patients were in age group of 18-40 years. In Group A, dizziness (n = 20) was the most common adverse effect associated with propranolol, while in Group B; tiredness (n = 3) and weight gain (n = 3) were the most common adverse effects associated with flunarizine. There was statistically significant increase in BMI after 2 months among patients who were in Group B than those who were in Group A (p=0.045). There was statistically significant difference in the mean (SD) Heart Rate value of participants in Group A (75.65± 5.1) and Group B (80.14 ± 5.9) at the end of 2nd month (p=0.001).Also, there was statistically significant improvement in headache frequency (p=0.01) headache intensity (p=0.004) and headache duration (p=0.04) in Group A as compare to Group B. Conclusion: Flunarizine was associated with fewer adverse effects and Propranolol was associated with low headache frequency, headache intensity and headache duration as compared to flunarizine group. Trial Registration: Clinical Trials Registry – India (CTRI) Number CTRI/2023/06/053593 [Registered on: 06/06/2023].