Failure to respond to antidepressants probably is the most common indication for electroconvulsive therapy (ECT). The literature seems to be divided as to whether medication resistance has a negative influence on the efficacy of subsequent ECT. Therefore, we performed a systematic review to investigate the effect of previous pharmacotherapy failure on the efficacy of ECT. Relevant cohort studies were identified from systematic search of the PubMed electronic database. Seven studies were included in this meta-analysis: the overall remission rate amounts to 48.0% (281/585) for patients with and 64.9% (242/373) for patients without previous pharmacotherapy failure. An exact analysis with the Mantel-Haenszel method (fixed effect model) shows a reduced efficacy of ECT in patients that received previous pharmacotherapy (OR, 0.52; 95% confidence interval [CI], 0.39-0.69). In conclusion, the efficacy of ECT is significantly superior in patients without previous pharmacotherapy failure as compared with medication-resistant patients. Because this finding is based on observational studies, it might be caused by a confounding factor, for example, the presence of psychotic features or the duration of the index episode. Electroconvulsive therapy seems to be an effective treatment for severely depressed patients as well as for patients with previous pharmacotherapy failure.