Aim: Infants with congenital heart disease and left-to-right shunts may develop significant clinical symptoms of congestive heart failure in spite of therapy with digoxin and diuretics. We investigated the effects of β-blockade in infants with severe heart failure. Methods and results: We performed a prospective, randomized, open monocenter trial in infants treated with digoxin and diuretics ( n=10) in comparison to 10 infants receiving additional β-blocker therapy. After 17 days on average β-blocker treated infants (propranolol:1,6 mg/kg/day) improved significantly with respect to Ross heart failure score (3.3±2.3 vs. 8.3±1.9, P=0.002), lower renin levels (338±236 vs. 704±490 μU/l, P=0.008) and lower mean heart rates in Holter ECG (118±10 vs. 142±11 beats/min, P<0.001). While digoxin and diuretic treated infants had unchanged mean heart rate (149±8 vs. 148±10 beats/min), less decrease of symptoms (Ross Score: 8.5±1.7 vs. 6.8±2.3, P=0.02) but a significant increase of renin levels (139±102 vs. 938±607 μU/l, P=0.001). Conclusion: Additional propranolol treatment but not digoxin and diuretics alone can effectively reduce clinical symptoms of heart failure in infants with congenital heart disease, who suffer from increased neurohormonal activation.