OBJECTIVES: A subgroup analysis of the Valsartan Heart Failure Trial (Val-HeFT) was performed to evaluate the effects of the angiotensin II receptor blocker, valsartan, in the patients with chronic heart failure (HF) not receiving angiotensin-converting enzyme (ACE) inhibitors. BACKGROUND: The ACE inhibitors reduce mortality and morbidity in patients with HF. Nonetheless, nearly 20% of potentially eligible patients may not be prescribed ACE inhibitors. RESULTS: Val-HeFT was an international, randomized, double-blinded trial that compared valsartan with placebo when added to the prescribed treatment of patients with HF. The two primary end points of the study were all-cause mortality and the composite of all-cause mortality and morbidity (sudden death with resuscitation, hospital admission for HF, or administration of intravenous inotropic or vasodilator drugs for ≥4 h without hospital admission). Of the 5,010 patients enrolled in the trial, 366 (7.3%) were not treated with ACE inhibitors at baseline. The effects of valsartan on the primary and secondary end points of the study were assessed in this subgroup of patients. RESULTS: Both all-cause mortality and combined mortality and morbidity for patients not treated with ACE inhibitors were significantly reduced in the valsartan treatment group compared with the placebo group (17.3% vs. 27.1%, p = 0.017 and 24.9% vs. 42.5%, p < 0.001, respectively). Consistent with the data on clinical events, patients randomized to valsartan showed improvements in physiologic variables, such as ejection fraction, left ventricular internal diameter in diastole, and plasma neurohormone levels. Permanent discontinuation of study treatment because of adverse experiences was comparable between the two groups. CONCLUSIONS: Val-HeFT has provided the first placebo-controlled outcome data demonstrating a favorable effect of an angiotensin receptor blocker on mortality and morbidity in patients with HF not treated with ACE inhibitors. Based on these results, valsartan appears to be an effective therapy in ACE inhibitor-intolerant patients.