Due to differences in treatment effect in studies on the effectiveness of digoxin in patients with congestive heart failure in sinus rhythm, a cross-over placebo-controlled, randomized double blind clinical trial was performed. Thirty one patients, without previous treatment with digoxin, in New York Heart Association (NYHA) functional class II to IV, with a dilated left ventricle and/or ventricular systolic dysfunction were included. Patients received digoxin, adjusted for blood levels, or placebo, during an 8 week period, prior to crossing over to the other treatment for another 8 weeks. The order of treatments was randomly allocated. Outcome measurement were performed at the end of each 8 week period. Digoxin, compared with placebo, improved NYHA class, 6.9% vs 41.4% (p = 0.013) and increased the treadmill exercise time, 406 +/- 204 s vs 484 +/- 185 s (p = 0.003). During the digoxin treatment the left ventricular and systolic diameter was reduced from 52.9 +/- 8.9 to 50.1 +/- 9.7 mm (p = 0.016) and the shortening fraction increased from 21.4 +/- 8.3 to 24.8 +/- 8.1% (p = 0.009). No significant difference was observed in the left ventricular end diastolic diameter (LVED) of the left ventricle and in a estimation of quality of life. In conclusion, digoxin treatment produced a significant improvement in functional capacity, exercise time, and left ventricular performance.