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To elucidate the mechanisms underlying nasolacrimal air regurgitation (AR) in the setting of continuous positive airway pressure therapy.Twelve nasolacrimal systems of 6 fresh female human cadavers were evaluated individually for AR using continuous positive airway pressure therapy before any nasolacrimal procedure. Cadavers were then randomly assigned to undergo nasolacrimal duct probing or endoscopic dacryocystorhinostomy and then each hemisystem was again evaluated for AR. The pressure where AR was first observed (discovery pressure) or maximum possible pressure in systems without AR was recorded. In systems that demonstrated AR, the pressure was then gradually decreased to the lowest pressure where regurgitation persisted. This pressure was recorded as the secondary threshold pressure.None of the 12 unoperated nasolacrimal systems or the 6 systems that underwent nasolacrimal duct probing demonstrated AR through the maximum continuous positive airway pressure therapy (30 cm H2O). After endoscopic dacryocystorhinostomy, all 6 nasolacrimal systems demonstrated AR. The mean discovery pressure was 16.0 cm H2O (range, 14.0–18.0 cm H2O) and mean secondary threshold pressure was 7.25 cm H2O (range, 6.5–8.0 cm H2O).Air regurgitation during continuous positive airway pressure therapy in the setting of prior endoscopic dacryocystorhinostomy can be replicated in a cadaver model. The secondary threshold pressures required for AR in this model were similar to AR pressures reported clinically. Prior to dacryocystorhinostomy, patients using continuous positive airway pressure therapy should be counseled on AR, and physicians should consider this phenomenon when evaluating ophthalmic complaints in postoperative patients on positive airway pressure therapy.