Uvulopalatopharyngoplasty (U3P) has been advocated for treatment of snoring and sleep apnea/hypopnea syndrome (SAHS), but often it does not effect a cure, so that other therapy (CPAP) is often required. We hypothesized that patients with U3P will have increased mouth air leak during CPAP because of loss of the soft palatal seal. This may result in decreased tolerance and compliance if CPAP therapy is required after U3P. We have therefore compared CPAP tolerance in 13 awake normal male subjects, 13 male patients with SAHS and 13 male patients treated with U3P, all naive to CPAP and matched for age and body mass index. All normal subjects and patients with SAHS were able to tolerate pressures of at least 20 cm H2O without mouth air leak or appreciable discomfort. In contrast male U3P patients started to leak air via the mouth at a mean CPAP pressure of 6.8 (SD, 2.4) cm H2O and were able to tolerate a mean maximal pressure of only 14.5 (SD, 2.6) cm H2O, which was significantly less than that in the other two groups (p < 0.001). We also examined nasal CPAP compliance (machine run time) in eight patients with SAHS who had previous U3P compared with 16 patients with SAHS without U3P. Both groups were matched for age, body mass index, and apnea/hypopnea index. Patients with U3P had significantly lower compliance (mean, 3.5 h/night) compared with patients without U3P (mean, 5.7 h/night), p = 0.01. We conclude that U3P may compromise nasal CPAP therapy by increasing mouth air leak and reducing the maximal level of pressure that can be tolerated.