Aim. To evaluate clinical relevance of differences between escitalopram and citalopram (equimolar) for major depressive disorder. ----- Methods. Review and meta-analysis of comparative randomized controlled trials (RCT). Comparisons were in relation to Montgomery-Asberg depression rating scale (MADRS) score reduction at weeks 1 (5 RCTs), 4 (5 RCTs), 6 (4 RCTs), 8 (5 RCTs), and 24 (1 RCT); proportion of responders at weeks 2, 4, 6 (2 RCTs for each time point), 8 (5 RCTs), and 24 (1 RCT); clinical global impression-severity (CGI-S) reduction at weeks 6 (1 RCT), 8 (5 RCTs), and 24 (1 RCT), and discontinuation due to adverse events or inefficacy during short-term (up to 8 weeks) and medium-term (24 weeks) treatment. ----- Results. MADRS reduction was greater with escitalopram, but 95% confidence intervals (CI) around the mean difference were entirely or largely below 2 scale points (minimally important difference) and CI around the effect size (ES) was below 0.32 ("small") at all time points. Risk of response was higher with escitalopram at week 8 (relative risk, 1.14; 95% CI, 1.04 to 1.26) but number needed to treat was 14 (95% CI, 7 to 111). All 95% CIs around the mean difference and ES of CGI-S reduction at week 8 were below 0.32 points and the limit of "small," respectively. Data for severe patients (MADRS>/=30) are scarce (only 1 RCT), indicating somewhat greater efficacy (response rate and MADRS reduction at week 8, but not CGI-S reduction) of escitalopram, but without compelling evidence of clinically relevant differences. Discontinuations due to adverse events or inefficacy up to 8 weeks of treatment were comparable. Data for the period up to 24 weeks are scarce and inconclusive. ----- Conclusion. Presently, the claims about clinically relevant superiority of escitalopram over citalopram in short-to-medium term treatment of major depressive disorder are not supported by evidence.