The aim of this study was to explore the significant predictors associated with electroconvulsive therapy (ECT) outcome for patients with major depressive disorder. Major depressive disorder inpatients (N=130) requiring ECT were recruited from a major psychiatric center in South Taiwan. ECT was generally performed for a maximum of 12 sessions. Symptom severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and Clinical Global Impression of Severity (CGI-S) before ECT, after every three ECT sessions, and after the last ECT. The generalized estimating equations method was used to analyze the influence of potential variables over time on the HAMD-17 and CGI-S, respectively. Fourteen patients not completing the first three sessions of ECT were excluded. The remaining 116 patients were included in the analysis. Patients with treatment-resistant depression, longer duration of the current depressive episode, and higher levels of pain were more likely to have less symptom reduction after acute treatment with ECT, irrespective of how the depressive symptoms were rated using HAMD-17 or CGI-S. To improve efficacy, earlier application of ECT and pain control should be considered during an acute course of ECT. Other clinical predictors related to ECT outcome require further investigation in future studies.