BACKGROUND: Primary acquired nasolacrimal duct obstruction (PANDO) is frequently encountered in perimenopausal women, causing tear flow stagnation and resulting in a variety of ocular discomfort symptoms. However, little is known about the alterations in the meibomian gland in postmenopausal women with PANDO. Hence, this study investigated the changes in the meibomian gland and ocular surface in postmenopausal women with PANDO. METHODS: This prospective study included 60 eyes of 60 postmenopausal women with PANDO (PANDO group) and 30 eyes of 30 postmenopausal women without PANDO (control group). The PANDO group was further subdivided into incomplete and complete PANDO groups, based on the degree of nasolacrimal duct obstruction. The patients' symptoms were evaluated using the ocular surface disease index questionnaire. The meibomian gland and ocular surface were assessed using the Keratograph 5 M. Other ophthalmologic examinations included the tear break-up time, corneal fluorescein staining, meibomian gland expression, and Schirmer I test. The correlations between the degree of nasolacrimal duct obstruction and other metrics were analyzed. RESULTS: The loss ratio of the upper eyelid was greater in the incomplete PANDO group than in the control group (p = 0.023). Meibomian gland distortion of the upper eyelid was more severe in the control group than in the complete PANDO group (p = 0.022). The non-invasive tear meniscus height was greater, whereas the intensity of corneal fluorescein staining was lower in the PANDO group than in the control group (all p < 0.05). The degree of nasolacrimal duct obstruction was positively associated with the non-invasive tear meniscus height and ocular surface disease index scores (p < 0.001 and p < 0.001, respectively). Corneal fluorescein staining and meibomian gland distortion of the upper eyelid were negatively correlated with the degree of nasolacrimal duct obstruction (p = 0.01 and p = 0.007, respectively). CONCLUSION: Postmenopausal women with PANDO exhibit significant morphological changes in the meibomian gland. More attention should be paid to meibomian gland loss in postmenopausal women with incomplete PANDO, as it is crucial for identifying meibomian gland impairments in patients with PANDO.