Nasal continuous positive airway pressure (N-CPAP) is now the treatment of choice for patients with sleep apnea syndrome (SAS). Side effects and adverse reactions have been described with this device. We have therefore systematically studied side effects of N-CPAP in 193 patients recruited consecutively from two French sleep centers (Lyon and Grenoble). Patients were followed up with repeated polysomnography, clinical assessment, and a formal questionnaire about subjective benefits and side effects of treatment. The patients (mean age, 59±12 years) were obese (body mass index, 32±7 kg/m2) and had been using N-CPAP for 19±17 months for moderate to severe SAS (respiratory disturbance index [RDI]=53±25/h). The clinical presentation was the same in the two sleep centers. Fifty percent of the patients complained of at least one side effect due to the nasal mask (allergy to the face, air leaks, abrasions of the ridge of the nose). Using individually molded masks, the patients exhibited fewer abrasions of the bridge of the nose (p<0.01) and had red eyes every morning in only 9% of cases vs 24% for the patients using industrial silicone nasal masks (p<0.025). Patients with silicone nasal masks also had more allergic reaction to the face (13% vs 5%), but this difference did not reach significance. Dry nose or mouth in the morning affected 65% of the patients. Sneezing and nasal drip were present in more than 35% of the subjects and nasal congestion in 25%. When the patients were separated in two groups, whether or not using a humidifier, no difference was found for any of the side effects described. The clinical presentation as to the clinical benefits obtained from N-CPAP were different when comparing mild vs moderate-to-severe SAS. However, no differences were shown in the two subgroups regarding the side effects due to the nasal mask. The discomfort of the N-CPAP apparatus in terms of noise was described more frequently in the subgroup with mild SAS. We did not observe any correlation between the side effects and the level of pressure used during N-CPAP. The rate of compliance remains high with a daily use of 6.5±3 h, with 88% of the patients using their device every night. This could be explained by the clinical benefit obtained: only 1% of the patients had no subjective benefit induced by their therapy. Snoring and daytime sleepiness were relieved in more than 65% of the subjects and sleep quality improved in 75%. In the present study, we have confirmed in two different centers in France that side effects were frequent during N-CPAP treatment. From this study, it also appears that the incidence of nasal side effects can be reduced with appropriate follow-up.