BACKGROUND: Escitalopram has shown efficacy and tolerability in the prevention of relapse in elderly patients with major depressive disorder (MDD). This post-hoc analysis compared time to relapse for young-old patients (n = 197) to that for old-old patients (n = 108). METHOD: Relapse prevention: after 12-weeks open-label treatment, remitters (MADRS ≤12) were randomised to double-blind treatment with escitalopram or placebo and followed over 24-weeks. Patients were outpatients with MDD from 46 European centers aged ≥75 years (old-old) or 65-74 years of age (young-old), treated with escitalopram 10-20 mg/day. Efficacy was assessed using the Montgomery Åsberg Depression Rating Scale (MADRS). RESULTS: After open-label escitalopram treatment, a similar proportion of young-old patients (78%) and old-old patients (72%) achieved remission. In the analysis of time to relapse based on the Cox model (proportional hazards regression), with treatment and age group as covariates, the hazard ratio was 4.4 for placebo versus escitalopram (χ(2)-test, df = 1, χ(2)= 22.5, p < 0.001), whereas the effect of age was not significant, with a hazard ratio of 1.2 for old-old versus young-old (χ(2)-test, df = 1, χ(2) = 0.41, p = 0.520). Escitalopram was well tolerated in both age groups with adverse events reported by 53.1% of young-old patients and 58.3% of old-old patients. There was no significant difference in withdrawal rates due to AEs between age groups (χ(2)-test, χ(2) = 1.669, df = 1, p = 0.196). CONCLUSIONS: Young-old and old-old patients with MDD had comparable rates of remission after open-label escitalopram, and both age groups had much lower rates of relapse on escitalopram than on placebo.