Cheyne-Stokes respiration (CSR) during sleep is common in patients with congestive heart failure (CHF). This pattern of breathing fragments sleep, leading to daytime symptoms of sleepiness and fatigue. It was hypothesized that by controlling CSR with noninvasive pressure preset ventilation (NPPV), there would be a decrease in sleep fragmentation and an improvement in sleep quality. Nine patients (eight males, one female; mean +/- SD 65 +/- 11 yrs) with symptomatic CSR diagnosed on overnight polysomnography (apnoea/hypopnoea index (AHI) 49 +/- 10 x h(-1), minimum arterial oxygen saturation (Sa,O2, 77 +/- 7%) and CHF (left ventricular ejection fraction 25 +/- 8%) were studied. After a period of acclimatization to NPPV (variable positive airway pressure (VPAP) II ST, Sydney, NSW, Australia and bilevel positive airway pressure (BiPAP), Murraysville, PA, USA), sleep studies were repeated on therapy. NPPV almost completely abolished CSR in all patients with a reduction in AHI from 49 +/- 10 to 6 +/- 5 x h(-1) (p<0.001). Residual respiratory events were primarily due to upper airway obstruction at sleep on-set. Arousal index was markedly decreased from 42 +/- 6 to 17 +/- 7 x h(-1) (p <0.001). Sleep architecture showed a trend toward improvement with a reduction in stage 1 and 2 (79 +/- 7% during the diagnostic night versus 72 +/- 10% during NPPV, (p=0.057)), whilst sleep efficiency, slow-wave sleep (SWS), and rapid eye movement (REM) were not altered. Controlling Cheyne-Stokes respiration with noninvasive pressure preset ventilation resulted in reduced arousal and improved sleep quality in the patients with congestive heart failure. Noninvasive pressure preset ventilation should be considered a potential therapy for Cheyne-Stokes respiration in congestive heart failure in those patients who do not respond or fail to tolerate nasal continuous positive airway pressure therapy.