Introduction:Electroconvulsive therapy (ECT) is an effective treatment for many mental disorders, especially severe and persistent depression, bipolar disorder, and schizophrenia. The aim of this study is to compare the effect of dexmedetomidine and alfentanil on agitation, satisfaction, seizure duration, and patients hemodynamic after ECT.Materials and Methods:In a three phase crossover randomized clinical trial, 75 patients aged between 18 and 50 years and candidate for ECT were enrolled and assigned into three groups (25 patients in each group). All patients, respectively, took premedication of dexmedetomidine, alfentanil, or saline in three consecutive phases. Patients received 0.5 μg/kg dexmedetomidine, 10 μg/kg alfentanil or normal saline intravenously, 10 min before induction. Finally, seizure and recovery duration, satisfaction and agitation score, and hemodynamic parameters were evaluated.Results:There was no significant difference about seizure duration, agitation score, and hemodynamic parameters between groups but recovery duration was significantly lower in the control group than dexmedetomidine (P = 0.016) and alfentanil group (P = 0.0001). Patients’ satisfaction was significantly higher in intervention groups (alfentanil and dexmedetomidine groups) (P = 0.0001).Conclusion:Given the equal effects of alfentanil and dexmedetomidine, it seems that choosing one of these two drugs for premedication of patients undergoing ECT is appropriate. Drug choice is influenced by numerous factors such as accessibility of each drug and the dominance of anesthesiologist and psychiatrist.