 In chronic heart failure CHF, endothelial function EF deterioration and muscle underperfusion elicit ergoreflex exercise oversignaling, hyperventilation and breathlessness. PDE5 inhibition, by improving EF, might be beneficial. We tested this hypothesis in a long-term therapeutic trial. CHF patients were randomly assigned to placebo 23 cases, group 1 or sildenafil 23 cases, group 2 in addition to their current antifailure therapy, for 6 months. In group 2 and not in group 1, assessments at 3 and 6 months showed the following changes: reduction of systolic pulmonary artery pressure -25.2 and 29.0 , ergoreflex effect on ventilation -66.6 and -72.5, ventilation to CO2 production slope VEVCO2, -14.0 and -16.0 and breathlessness -29.6 and -27.1; increase of brachial artery flow-mediated dilatation FMD, 57.6 and 67.0, peak exercise O2 uptake peak VO2, 25.0 and 26.3 and ratio of VO2 to work rate changes VO2WR, 20.7 and 22.0. These changes were significant at p0.01. In group 2 and not in group 1, a significant correlation was found, at 3 and 6 months, between changes in FMD and those in ergoreflex VE. Changes in ergoreflex correlated with those in peak VO2 and VEVCO2 slope. No remarkable side effects were noted, but flushing in 3 patients. 