To investigate the effect of uvlopalatopharyngoplasty (UPPP) on post-surgery continuous positive airway pressure (CPAP) treatment during sleep in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Thirty-one OSAHS patients after UPPP surgery were recruited and studied on for more than 12 months after the procedure. Among them, 24 patients were treated with classical UPPP (cUPPP), which removes all of uvula and part of the soft palate. Seven had modified UPPP (mUPPP), keeping part of the uvula. The control group was 31 years in age, body mass index (BMI) and apnea-hypopnea index (AHI) matched, and newly diagnosed OSAHS patients without prior treatment. A manual titration of CPAP was performed during both (NREM) and non-rapid eye movement (NREM) sleep in all 62 patients. Patients were asked to keep a supine position while sleeping during the test. When significant mouth air leakage occurred and/or titration worsened with an increase of CPAP pressure, the pressure level was considered as the highest CPAP (hCPAP) a patient can tolerate in that sleep stage. The CPAP machine used for titration could produce highest pressure at 20 cm H2O. There were 74% (23/31) of UPPP patients who had less than 50% decrease in AHI, and 84% (26/31) of the 31 patients still had AHI>15 (range 16-110) during post-operation polysomnography (PSG) test. Most of them need further CPAP therapy. All of the untreated OSAHS patients could tolerate 17-20 cm H2O of CPAP during sleep. None had severe mouth air leak before an optimal pressure was reached. In contrast, four in the surgery group failed to respond to CPAP treatment during both NREM and REM sleep and one more during REM sleep. All of the seven patients who had a mUPPP could tolerate CPAP. One of the three tested both before and after surgery failed in the CPAP treatment after surgery during REM sleep. UPPP may compromise nasal CPAP therapy in OSAHS, especially in procedures with greater resection of the soft palate.