The improved cardiac function in patients with congestive heart failure treated with coenzyme Q10 supports the hypothesis that this condition is characterized by mitochondrial dysfunction and energy starvation, so that it may be ameliorated by coenzyme Q10 supplementation. However, the main clinical problems in patients with congestive heart failure are the frequent need of hospitalization and the high incidence of life-threatening arrhythmias, pulmonary edema, and other serious complications. Thus, we studied the influence of coenzyme Q10 long-term treatment on these events in patients with chronic congestive heart failure (New York Heart Association functional class III and IV) receiving conventional treatment for heart failure. They were randomly assigned to receive either placebo (n = 322, mean age 67 years, range 30-88 years) or coenzyme Q10 (n = 319, mean age 67 years, range 26-89 years) at the dosage of 2 mg/kg per day in a 1-year double-blind trial. The number of patients who required hospitalization for worsening heart failure was smaller in the coenzyme Q10 treated group (n = 73) than in the control group (n = 118, P < 0.001). Similarly, the episodes of pulmonary edema or cardiac asthma were reduced in the control group (20 versus 51 and 97 versus 198, respectively; both P < 0.001) as compared to the placebo group. Our results demonstrate that the addition of coenzyme Q10 to conventional therapy significantly reduces hospitalization for worsening of heart failure and the incidence of serious complications in patients with chronic congestive heart failure.