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Short-term quality improvement (QI) interventions for depression can improve long-term mental health but mechanisms are unknown. We hypothesized that 1 pathway for such health benefits was an indirect effect with QI reducing risk factors for depression such as stressful life events.To determine whether 6–12 month QI programs for depression reduce negative life events at 5-year follow-up and to model the relationship between program implementation, life events and mental health over 9 years.Forty-six primary care clinics in 6 managed care organizations were randomized to usual care or 1 of 2 QI interventions. We focus on the intervention that provided resources to assess and manage depression while particularly facilitating access to evidence-based psychotherapy (“QI-Therapy”).A total of 1300 enrolled patients with current depressive symptoms, who had data at any of 4 data points: baseline, or follow-up year 1, 5, or 9.Total and negatively-evaluated life events and psychologic well-being.A path model showed that QI-Therapy, in addition to improving psychologic well-being at year 1 (P = 0.0033), reduced negative life events at year 5 (P = 0.0033). This effect was not fully explained by improved psychologic well-being. Better mental health (P < 0.0001) and fewer negative life events (P = 0.0013) at year 5 were associated with improved psychologic well-being at 9 years.Depression QI programs that include resources for psychotherapy can reduce occurrence of life events, further protecting subsequent mental health. Implications for the design of QI programs and development of prevention interventions are discussed.