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Despite major advances in treatment congestive heart failure (CHF) is still one of the major causes of morbidity and mortality. Coenzyme Q10 is a naturally occurring substance that has antioxidant and membrane stabilizing properties. Administration of coenzyme Q10 in conjunction with standard medical therapy has been reported to augment myocardial kinetics, increase cardiac output, elevate the ischemic threshold, and enhance functional capacity in patients with congestive heart failure. The aim of this study was to investigate some of these claims. Seventeen patients (mean New York Heart Association functional class 3.0 ± 0.4) were enrolled in an open-label study. After 4 months of coenzyme Q10, therapy, functional class improved 20% (3.0 ± 0.4 to 2.4 ± 0.6, p < 0.001) and there was a 27% improvement in mean CHF score (2.8 ± 0.4 to 2.2 ± 0.4, p< 0.001). Percent change in the resting variables included the following: left ventricular ejection fraction (LVEF), +34.8%; cardiac output, +15.7%; stroke volume index, +18.9%; end-diastolic volume area, −8.4%; systolic blood pressure (SBP), −4.4%; and Emax, (SBP end-systolic volume index [ESVI]) +11.7%. MVo2 decreased by 5.3% (31.9 ± 2.6 to 30.2 ± 2.4, p = NS). Therapy with coenzyme Q10 was associated with a mean 25.4% increase in exercise duration and a 14.3% increase in workload. Percent changes after therapy include the following: exercise LVEF, +24.6%; cardiac output, +19.1%; stroke volume index, +13.2%; heart rate, +6.5%; SBP, −4.3%; SBP ESVI, +18.6%; end-diastolic volume (EDV) area, −6.0%; MVo2, −7.0%; and ventricular compliance (% δ SV EDV) improved <100%. In summary, coenzyme Q10 therapy is associated with significant functional, clinical, and hemodynamic improvements within the context of an extremely favorable benefit-to-risk ratio. Coenzyme Q10 enhances cardiac output by exerting a positive inotropic effect upon the myocardium as well as mild vasodilatation.