AIM: To explore the pathogenesis of asymmetric primary open angle glaucoma (POAG) in both eyes by comparing the intraocular pressure (IOP) of patients who sleep in different positions and to investigate the relationship between IOP variations and sleep positions. METHODS: One hundred and thirty-one patients with asymmetric POAG and forty-six healthy volunteers were enrolled. All participants completed a questionnaire that provided information about their sleep laterality. The cup disc ratio (C/D) and visual field defect established binocular asymmetry. The IOP of both eyes was measured using iCare parameters after the patients were asked to change body position. The “worse” and “better” eyes were identified according to the diagnosis, whereas the “dependent” and “independent” eyes were defined according to the lateral position. RESULTS: No significant difference in sleep laterality was observed between healthy people and patients with POAG (F=3.195, P=0.362). Among the enrolled patients, the IOP of the dependent eye was always greater than that of the independent eye in the lateral position (P<0.05). In the patients with binocular asymmetric POAG, the questionnaire clearly showed that 85.7% of left side preferences were found their left eyes to be the worse eyes and the right eyes of 71.4% patients with a right side preference were the more serious. When the asymmetric C/D ratio was greater than or equal to 0.2, the worse eye of patients with POAG and a preferred sleeping position was the dependent eye (χ2=16.762, P=0.001). CONCLUSION: A higher IOP was measured in the dependent eye in the lateral position. The long-term tendency to choose a lateral sleeping position might lead the dependent eye to manifest more severe symptoms than the independent eye. Thus, the lateral sleeping position might be one cause of asymmetric POAG.