Costs of care for heart failure are high, but it is unclear what factors contribute to these costs. In this study, 1098 health maintenance organization patients were evaluated following a first hospitalization with a primary diagnosis of heart failure. Depression and heart failure status were determined through diagnostic, laboratory, and pharmacy records. Actual utilization and cost values were derived from administrative data. After adjusting for age, sex, medical comorbidity, and length of stay at index hospitalization (as proxy for heart failure severity), costs were 26% higher in the antidepressant group and 29% higher in the depression diagnosis group compared with the no depression group (both P<.001). Increased inpatient and outpatient utilization both contributed to the increased costs. Depression may make a significant contribution to the high costs of care for heart failure.