A previous uncontrolled study suggested that nasal continuous positive airway positive airway pressure (NCPAP) may improve left ventricular ejection fraction (LVEF) in patients with congestive heart failure (CHF) and Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). In order to more critically evaluate the effects of NCPAP on cardiac function, we undertook a randomized, controlled trial of NCPAP in 29 patients with heart failure and CSR-CSA over a 3-mo period, with LVEF as the primary outcome measure. Patients with CHF and associated CSR-CSA who were receiving optimal medical therapy were randomly assigned to a control group (n = 15) or a group receiving nightly NCPAP (n = 14). Twelve patients in each group completed the study. There was a greater improvement of LVEF in the NCPAP group than in the control group during the study (mean +/- SEM = 7.7 +/- 2.5 versus - 0.5 +/- 1.5%, p = 0.019). In addition, there was a significantly greater reduction in the number of apneas and hypopneas (-28.5 +/- 3.9 versus -6.1 +/- 7.0 per hour of sleep, p = 0.012) in the NCPAP group than in the control group. Significantly greater improvements in symptoms of fatigue (5.6 +/- 1.2 versus 0.8 +/- 0.7, p = 0.005) and disease mastery (3.6 +/- 1.1 versus -0.7 +/- 0.7, p = 0.031) were also observed in the NCPAP group. We conclude that in patients with chronic heart failure and CSR-CSA, nightly administration of NCPAP can attenuate CSR-CSA, improve cardiac function, and alleviate symptoms of heart failure.