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Depression is associated with poor prognosis in patients with cardiovascular disease (CVD). We hypothesized that depressive symptoms at discharge from a cardiac rehabilitation program are associated with an increased risk of future CVD-related hospitalizations.We examined 486 CVD patients (mean age = 59.8 ± 11.2) who enrolled in a comprehensive 3-month rehabilitation program and completed the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). At follow-up we evaluated the predictive value of depressive symptoms for CVD-related hospitalizations, controlling for sociodemographic factors, cardiovascular risk factors, and disease severity.During a mean follow-up of 41.5 ± 15.6 months, 63 patients experienced a CVD-related hospitalization. The percentage of depressive patients (HADS-D ≥8) decreased from 16.9% at rehabilitation entry to 10.7% at discharge. Depressive symptoms at discharge from rehabilitation were a significant predictor of outcome (HR 1.32, 95% CI 1.09-1.60; p = 0.004). Patients with clinically relevant depressive symptoms at discharge had a 2.5-fold increased relative risk of poor cardiac prognosis compared to patients without clinically relevant depressive symptoms independently of other prognostic variables.In patients with CVD, depressive symptoms at discharge from rehabilitation indicated a poor cardiac prognosis.