B-type natriuretic peptide (BNP) is a cardiac neurohormone used as a noninvasive tool for diagnosing and monitoring heart failure. Beta blockers have beneficial effects in patients with heart failure as well as a direct effect on BNP plasma levels. The aim of this study is to compare the efficacy of a BNP-guided approach vs. standard care on beta-blocker titration in heart failure patients. Forty-one patients with heart failure were randomized into a clinical trial. Bisoprolol was started, and the dose was regularly up-titrated. BNP was measured monthly. The clinical group had beta-blocker dosage increased according to standard care, whereas the BNP group had beta-blocker dosage up-titrated according to plasma BNP levels plus standard care. The primary outcome was mean beta-blocker dose achieved after 3 months. BNP levels, left ventricular ejection fraction, clinical score, quality of life, and hospitalization were collected in all patients. BNP-guided up-titration of beta blocker in ambulatory patients with heart failure did not result in higher doses of beta blocker at the end of 3 months+/-SD (5.9+/-4.3 mg vs. 4.4+/-3.4 mg, p=0.22). Left ventricular ejection fraction was significantly improved in both groups by 7.3% (95% confidence interval, 4.1%-10.4%; p<0.0001). A trend toward better quality of life was seen in the BNP group.