Abstract: In contrast to “remission” from an episode of major depressive disorder (MDD), for which there is general agreement in the literature, the optimal definition of “recovery” from MDD is uncertain. Previous definitions of recovery have used inconsistent thresholds for symptom severity and duration of wellness. To address the effects of duration and degree of recovery from an episode of MDD on recurrence risk, and the impact of maintenance antidepressant treatment on recurrence, we analyzed 258 patients from a randomized, double-blind study of outpatients with recurrent MDD. All patients had responded to 8½ months of venlafaxine extended release and were subsequently randomized to receive venlafaxine ER or placebo during 2 consecutive 12-month maintenance phases. Four definitions of recovery were used to evaluate recovery rates and time to recurrence: (1) 17-item Hamilton Depression Rating Scale (HAM-D17) total score ≤3 with duration ≥120 days; (2) HAM-D17 ≤3 with duration ≥56 days; (3) HAM-D17 ≤7 with duration ≥120 days; and (4) HAM-D17 ≤7 with duration ≥56 days. Recovery definitions using lower symptom severity and longer duration thresholds produced lower rates of recurrence. Patients on placebo were more likely to have a recurrence than patients on venlafaxine ER, with hazard ratio (HR) ranging from 2.5 among patients who recovered by the most relaxed criteria (definition 4), to 5.3 among patients who recovered by the most stringent criteria (definition 1). We conclude that protection against recurrence derives from the degree and duration of recovery, particularly for patients maintained on antidepressant medication.