OBJECTIVE: Continuous Positive Airway Pressure (CPAP) is the gold standard treatment for OSA. A wide variety of masks are used during CPAP therapy. The aim of the study is to compare polysomnography outcomes during titration for different types of masks (oronasal, nasal and pillow) and assess the impact on PAP titration. METHODS: We retrospectively analyzed all CPAP titration polysomnography for one year. Anthropometric data and baseline apnea severity were documented. RESULTS: A total of 497 patients were evaluated. Nasal masks were used in 82.3% (n = 409), pillow in 14.1% (n = 70) and oronasal in 3.6% (n = 18). There was no difference according to body mass index and baseline apnea-hypopnea index among the groups. The oronasal group was older and had higher titrated CPAP pressure, higher residual apnea-hypopnea index, lower sleep efficiency, more superficial N1 sleep and longer wake time after sleep onset. All other polysomnography outcomes were similar among the groups. The mean CPAP level was 11.6 ±â€¯2.1 cm H2O for the oronasal mask, 10.1 ±â€¯2.1 cm H2O for the nasal mask and 9.8 ±â€¯2.2 cm H2O for the pillow. The residual apnea-hypopnea index was 10.4 ±â€¯7.9 for the oronasal mask, 5.49 ±â€¯5.34 events/h for the nasal mask and 4.98 ±â€¯5.48 events/h for the pillow. The baseline apnea-hypopnea index was correlated with of a higher CPAP pressure for all the groups (p < 0.001 for the nasal group, p = 0.001 for the pillow group and p = 0.049 for the oronasal group). Body mass index and residual AHI were correlated with of a higher CPAP pressure for the nasal and pillow groups only (p < 0.001). CONCLUSION: The interface can have a significant impact on the effectiveness of PAP titration. Patients with oronasal masks have higher CPAP pressure, higher residual apnea-hypopnea index, lower sleep efficiency and higher wake time after sleep onset. Oronasal masks should not be recommended as the first choice for apnea patients. LEVEL OF EVIDENCE: Level 3.