This intervention study conducted in the Neurology outpatient Department of Mymensingh Medical College Hospital (MMCH) from January 2006 to December 2007 to compare efficacy of amitriptyline, pizotifen and propranolol in the prophylaxis of migraine. Ninety cases were selected following certain inclusion and exclusion criteria. Result showed that the differences in duration, frequency and severity of attack were reduced in all groups but the differences among the groups were not significant (p>0.05). However, compared with amitriptyline and pizotifen, the propranolol group needed tablet paracetamol as abortive therapy less frequently which was statistically significant (p<0.05). All the drugs were well tolerated with minimum adverse effects.