The aim of this study is to assess the effects of short- and long-term exposure to hyperbaric oxygen (HBO) on nasal mucociliary clearance (MCC). This study included 47 consecutive nondiabetic patients treated with hyperbaric oxygen therapy (HBOT). Participants were divided into 2 groups according to the taken number of HBOT sessions. Nineteen patients who received <11 HBOT sessions comprised short-term HBOT group, 28 patients who received more than 15 sessions comprised the long-term HBOT group. Mucociliary clearance was measured using a saccharin clearance test, which was performed 3 times on patients: prior to, at completion of, and 6 months after HBOT. The average number of HBOT sessions was 8 ± 1.9 in short-term HBOT group and 20 ± 4.8 in long-term group. Both short- and long-term exposure to HBO led to significant influence on MCC upon treatment completion (both P < 0.001). In addition, only long-term exposure to HBO caused significant elongation of MCC at long-term evaluation (6 months after HBOT). From these objective measurements, the authors can conclude that long-term exposure to HBO can cause irreversible damage to MCC compared with short-term exposure and HBOT appears to affect MCC in a dose-dependent manner. The clinical significance of this effect is of concern for patients undergoing HBOT for middle ear, sinonasal, or respiratory tract infections. Patients who undergo chronic HBOT should be monitored closely and informed about the possible negative effects.