This post-hoc analysis evaluated long-term psychosocial outcomes in patients with recurrent major depressive disorder treated with venlafaxine extended release (ER) 75–225 mg/day or placebo. Patients who responded to 10-week venlafaxine ER 75–300 mg/day treatment and maintained response through a 6-month continuation treatment were assigned randomly to venlafaxine ER or placebo maintenance-phase treatment. Data from responders to acute and continuation venlafaxine ER 75–225 mg/day treatment were analyzed during 12-month maintenance treatment while receiving venlafaxine ER of up to 225 mg/day. Failure to maintain improvement in psychosocial functioning, on the basis of the Social Adjustment Scale-Self-Report, Life Enjoyment Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and Short-Form Health Survey, was defined as loss of at least 50% of the improvement from acute-phase baseline achieved during acute and continuation treatment or dose escalation of more than 225 mg/day. The probability of remaining well (no failure to maintain improvement in functioning) was significantly higher through 12-month maintenance treatment for patients treated with venlafaxine ER 75–225 mg/day versus placebo Social Adjustment Scale-Self-Report, Life Enjoyment Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, and Short-Form Health Survey component summary scores (all P≤0.0351). Effects of up to 20 months of treatment with venlafaxine ER 75–225 mg/day on psychosocial functioning were consistent with the results for venlafaxine ER 75–300 mg/day.