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Purpose: To evaluate the incidence and risk factors for inflammatory conditions among patients with primary acquired nasolacrimal duct obstruction (PANDO)., Methods: A retrospective case-control study was conducted among patients of Clalit Health Services (CHS) in Israel from 2001 to 2022. For each case, three controls were matched among all CHS patients according to year of birth, sex, and ethnicity. Differences in demographic characteristics, ocular surface, eyelid, upper airway, and systemic diseases were assessed between the groups, and odds ratios (OR) were calculated., Results: A total of 60,726 patients diagnosed with PANDO were included. The average age of PANDO patients was 63 ± 18 years, 63% were female. Significant associations were found between PANDO and various ocular surface and eyelid conditions, including chronic conjunctivitis (OR 2.96, 95% CI [2.73-3.20]), vernal keratoconjunctivitis (OR 2.89, 95% CI [2.45-3.29]), and blepharitis (OR 2.75, 95% CI [2.68-2.83]). There was a significant association with various upper airway conditions, including rhinitis (OR 1.62, 95% CI [1.58-1.66]), chronic sinusitis (OR 1.71, 95% CI [1.62-1.80]), and deviated nasal septum (OR 1.76, 95% CI [1.69-1.84]). Association was also observed with systemic conditions, including asthma (OR 1.34, 95% CI [1.27-1.41]) and atopic dermatitis (OR 1.36, 95% CI [1.32-1.41])., Conclusion: Ocular surface, eyelid, upper airway, and systemic inflammatory-related diseases were found to be associated with PANDO, supporting the theory that inflammation has a prominent role in the pathophysiology of PANDO., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)