Five healthy buffalo calves were used in this study in a crossover design with an interval of three weeks. In group I, the five calves received medetomidine 10 µg/kg intravenously while in group II, the same five calves, after three weeks, were injected i.v. with romifidine 50 µg/kg. The calves were evaluated at baseline and then at 5, 15, 30, 45, 60, 75 and 90 minutes after drug administration for respiratory rate, heart rate, degree of sedation, muscle relaxation, and response to pedal and        pinprick reflexes. Weak time, down time and recovery time were        recorded in both groups. ECGs were recorded in all animals at baseline, 5, 10, 15, 30, 45 and 60 min post-injection. Blood samples were taken at baseline, 5, 15, 30, 60 and 90 minutes after drug administration for     determination of serum glucose, urea, AST, LDH and CPK. Heart rate decreased significantly in both groups. ECG findings in group I revealed increase in the amplitude of R wave and T waves became monophasic and had higher amplitude while in group II there was an atrioventricular (AV) heart block. Moderate sedation, mild muscle relaxation and mild analgesia were recorded in both groups. There was significant increase in serum glucose in both groups, while group II only showed significant increase in serum urea. Serum AST,LDH and CPK increased            significantly in both groups compared to baseline values. It could be concluded that medetomidine and romifidine are considered beneficial for safe investigation and clinical examination in buffalo calves but    further restraint or conjunction with other local or general anesthetic is needed for surgical approaches. However, medetomidine is considered superior to omifidine because the later induces prolonged                    cardiopulmonary depression and comparatively higher serum levels of urea and cardiac enzymes.