We conducted a systematic review and meta-analysis to investigate the comparative effectiveness of ketamine versus electroconvulsive therapy (ECT) for the treatment of major depressive episodes (MDEs). PubMed, EMBASE and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) comparing ketamine and ECT for MDE. The primary outcome was response rate, for which we prespecified a non-inferiority margin of -0.1, based on the largest and most recent RCT. Response was defined as a reduction of at least 50 % in the depression scale score. Six RCTs met the inclusion criteria, comprising 655 patients. In the overall population, ketamine was not non-inferior to ECT in response rate (RD -0.10; 95 % CI -0.26 to 0.05; p = 0.198; I = 72 %). The ECT group had a higher reduction in depression scores, but without difference in remission and relapse rates. Regarding safety outcomes, ketamine had better posttreatment cognition scores and reduced muscle pain rate compared with ECT, albeit with an increased rate of dissociative symptoms. In a subanalysis with only inpatients, ketamine was inferior to ECT in response rate (RD -0.15; 95 % CI -0.27 to -0.03; p = 0.014; I = 25 %), remission, and change in depression scores. These findings support the use of ECT over ketamine for inpatients. Further RCTs are warranted to clarify the comparative effect of these treatments for outpatients.