Role of propranolol and cyproheptadine in the prophylaxis of migraine was studied in a controlled double blind trial. Two hundred fifty-nine patients were divided into four groups. Each group was either given a placebo, cyproheptadine, propranolol or a combination of the latter two drugs. The patients were followed for a period of three months. Significant relief in frequency, duration and severity from migranous attacks was seen in all drug treated groups over placebo. Significant correlation in response was seen in frequency, duration and severity in all the groups which received drugs. Statistically more significant relief was seen in cyproheptadine and propranolol treated group as compared to individual drug treated groups. In cyproheptadine and propranolol treated groups, the dropout rate was lower and associated symptoms were better relieved than in other groups. The study shows efficacy of combination of cyproheptadine and propranolol in migraine prophylaxis.