BACKGROUND: Hospitalizations for ambulatory caresensitive conditions (ACSCs), conditions that should not require inpatient treatment if timely and appropriate ambulatory care is provided, may be an important contributor to rising healthcare costs and public health burden. OBJECTIVE: To examine if probable major depression is independently associated with hospitalization for an ACSC in patients with diabetes. DESIGN: Secondary analysis of data from a prospective cohort study. PARTICIPANTS: Population-based cohort of 4,128 patients with diabetes ≥ 18 years old seen in primary care, who were enrolled between 2000 and 2002 and followed for 5 years (through 2007). MAIN MEASURES: Depressive symptoms were assessed with the Patient Health Questionnaire-9. Outcomes of interest included time to initial hospitalization for an ACSC and total number of ACSC-related hospitalizations. We used Cox proportional hazards regression models to ascertain an association between probable major depression and time to ACSC-related hospitalization, as well as Poisson regression for models examining probable major depression and number of ACSC-related hospitalizations. KEY RESULTS: Patients' mean age at study enrollment was 63.4 years (Standard Deviation: 13.4 years). Over the 5-year follow-up period, 981 patients in the study were hospitalized a total of 1,721 times for an ACSC, comprising 45.1 % of all hospitalizations. After adjusting for baseline demographic, clinical and health-risk behavioral factors, probable major depression was associated with initial ACSC-related hospitalization (Hazard Ratio: 1.41, 95 % Confidence Interval [95 % CI]: 1.15, 1.72) and number of ACSC-related hospitalizations (Relative Risk: 1.37, 95 % CI: 1.12, 1.68). CONCLUSIONS: Probable major depression in patients with diabetes is independently associated with hospitalization for an ACSC. Additional research is warranted to ascertain if effective interventions for depression in patients with diabetes could reduce the risk of hospitalizations for ACSCs and their associated adverse outcomes.