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One of the strongest predictors of depression recurrence in those who respond to treatment is the presence of residual depressive symptoms. Our goal was to examine stressful life event exposure as a mechanism of recurrence in previously depressed patients with residual depression symptoms. That is, we predicted that higher levels of residual symptoms will significantly predict exposure to acute life events that will then heighten prospective recurrence risk.Participants included 68 adult outpatients with major depression (42 women; age 18–60) who completed a 12-month naturalistic follow-up after achieving remission in a 20-week randomized, open label trial of interpersonal psychotherapy, cognitive-behavioral therapy, or antidepressant medication. Depression recurrence was defined as the reemergence of an episode of major depression as determined by structured interview. Acute life events and chronic stressors were assessed at the end of follow-up using a contextual interview.Posttreatment depression scores significantly prospectively predicted an increased risk for recurrence, and acute life events in the follow-up period. Cox regression survival analyses modeling life events as time-dependent covariates showed that life event exposure mediated the relation of residual symptoms to recurrence even controlling for chronic stress.Our findings implicate residual symptoms in heightening depression recurrence risk through exposure to stressful life events. Depression recurrence adds significantly to the burden of the disorder. Therefore, rigorous follow-up of patients targeting the stressful context has the potential to prevent a lifelong pattern of illness.