The long-term beneficial effects of pimobendan in the treatment of chronic heart failure (CHF) have not been established, so the present trial compared pimobendan (1.25 or 2.5 mg twice daily) vs placebo in 306 patients with stable New York Heart Association class IIm or III CHF, and a radionuclide or echocardiographic left ventricular ejection fraction (LVEF) ≤45% despite optimal treatment with conventional therapy, for up to 52 weeks in a double-blind protocol. At the end of the 52 weeks of treatment, combined adverse cardiac events had occurred in 19 patients in the pimobendan group (15.9%) vs 33 patients in the placebo group (26.3%). The cumulative incidence of combined adverse cardiac events was 45% lower (95% confidence interval of hazard ratio: 0.31-0.97, log-rank test: p=0.035) in the pimobendan group than in the placebo group. Death and hospitalization for cardiac causes occurred in 12 patients in the pimobendan group (10.1%), vs 19 patients in the placebo group (15.3%), but without significant difference. Treatment with pimobendan also increased the mean Specific Activity Scale score from 4.39±0.12 at baseline to 4.68±0.15 at 52 weeks (p<0.05). In conclusion, long-term treatment with pimobendan significantly lowered morbidity and improved the physical activity of patients with mild to moderate CHF. (Circ J 2002; 66: 149 - 157)