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To measure pharyngeal wall floppiness (PWF) under different pressures, a novel method and technique were introduced in the present study.A prospective clinical study.Forty-seven healthy subjects (32 male; mean age, 37.9 years) and 49 patients with obstructive sleep apnea syndrome (OSAS) (46 male; mean age, 41.45 years) were recruited. The pharyngeal cavity volume was measured by acoustic reflection under positive (10 cm H2O) and negative (−10 cm H2O) pressures. The pharyngeal cavity volume was detected from the segment of 10 to 20 cm from the incisor. Moreover, PWF was calculated from the difference of pharyngeal cavity volumes under positive and negative pressures divided by the sum of the volumes under positive and negative pressures. The measurements were conducted on a group of 7 subjects weekly over 3 consecutive weeks to evaluate test-retest variability.The mean PWF was 0.19 ± 0.11 in healthy subjects and 0.24 ± 0.07 in the OSAS group, with a significant difference (P < .01). There was moderate positive correlation between PWF and age or body mass index in healthy subjects. In the 7 subjects, the mean measured interclass correlation coefficient was 0.9 (P < .05) in 3 consecutive weekly measurements.The OSAS population had greater PWF compared to healthy subjects. The age dependency of PWF in healthy subjects implied which might play important roles in the development of OSAS. This noninvasive and reproducible technique might be a useful tool in OSAS clinical applications.