Diuretic use is associated with activation of neurohormones and disease progression in heart failure. Yet, diuretics are commonly prescribed, although little is known about their long-term effects. We performed a study based on propensity score matching, which indicated that in subjects with ambulatory, chronic, mild-to-moderate heart failure, diuretic use was associated with increased mortality and hospitalization. These findings call into question the wisdom of using long-term diuretic therapy in heart failure patients who are asymptomatic or minimally symptomatic.