This pooled analysis evaluated the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) for the treatment of major depressive disorder (MDD) in patients grouped by age and sex. Nine clinical trials were pooled. Outpatients 18 years or older with MDD received desvenlafaxine 50, 100, 200, or 400 mg/d (men = 709; women = 1096) or placebo (men = 399; women = 709) for 8 weeks. Data were analyzed by sex and by age groups of 40 years and younger, 41 to 54 years, 55 to 64 years, and 65 years and older. The primary outcome was change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score at the final evaluation. Secondary measures included response (≥50% reduction in HAM-D17) and remission (HAM-D17 ≤7). No significant sex-treatment, age-treatment, or sex-age-treatment interactions were observed. Differences in the HAM-D17 change from baseline for desvenlafaxine versus placebo were −1.72 for women (P < 0.001) and −2.11 for men (P < 0.001); these changes were significant among women of the 18-to-40 (P = 0.01), 41-to-54 (P = 0.002), and 65-years-and-older subgroups (P = 0.02), and significant among men for the 18-to-40 (P = 0.03) and 41-to-54 subgroups (P = 0.002). The response rates for desvenlafaxine and placebo were 53% and 42% (P < 0.001), respectively, among women, and 53% and 41% (P < 0.001), respectively, among men; the remission rates were 31% and 21% (P < 0.001) and 34% and 26% (P = 0.007), respectively. The response rates were similar across age subgroups, with significant differences from placebo observed in the 18-to-40 (P ≤ 0.05), 41-to-54 (P ≤ 0.005), and 65-and-older subgroups (P = 0.02). The remission rates were significant versus placebo in the 41-to-54 (P = 0.006), 55-to-64 (P = 0.01), and 65-and-older (P = 0.02) subgroups among women but not in any age subgroup among men. Desvenlafaxine generally improved depressive symptoms across age and sex subgroups.