Abstract We evaluated the role of clinical, BNP and echocardiographic left ventricular (LV) indices in predicting the development of acute heart failure (HF) following beta-blocker initiation and uptitration in 50 stable CHF patients with LVEF < 40% and creatininemia < 250 μmol/l. Use of NYHA class alone predicted the development of acute HF decompensation in only 56% and the absence of this event in 93% of patients. Use of echocardiographic indices (systolic PAP < 40 mmHg or E/A ratio < 1.4 or EDT > 145 ms) predicted the absence of acute HF decompensation in 100% of patients. Use of NYHA > 3 combined with BNP > 398 pg/ml or with echocardiographic indices (i.e. systolic PAP > 40 mmHg or E/A > 1.4 or EDT < 145 ms) predicted the development of acute HF decompensation in 100% of patients. In conclusion use of BNP and echocardiographic LV filling pressure indices in combination with NYHA class may predict beta-blocker tolerance more accurately than clinical indices alone in patients with LV systolic dysfunction (LVEF < 40%).