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Abstract The aim was to investigate the incidence, clinical presentation, and potential risk factors for suspected dorzolamide-induced blepharitis (DIB), in dogs diagnosed with glaucoma or hereditary glaucoma predisposition. A retrospective review was conducted using clinical records of 286 dogs with primary or secondary glaucoma, or a hereditary predisposition to glaucoma (goniodysgenesis), that received dorzolamide eye drops between October 1, 2012, and January 1, 2020. Cases of suspected DI B were identified based on resolution of blepharitis following drug withdrawal. Statistical analysis, including odds ratio calculations, was performed to assess the potential risk factors. Eighteen dogs (6.2%) developed DIB after dorzolamide use. The median time before the development of DI B was 60 days. A significant association was identified between dogs with a history of seasonal skin allergies and the development of blepharitis (odds ratio: 12.4, 95% CI: 4.04–35.3, p < 0.001). However, no significant association was found with prior intraocular surgery ( p = 0.26) or dry eye disease ( p = 0.19). Clinical symptoms resolved within a median of 60 days after discontinuing dorzolamide, and most dogs were successfully switched to brinzolamide without recurrence of symptoms. Seasonal allergies seem to be a significant risk factor for development of DI B. Dorzolamide is one of the most frequently used drugs for treatment of glaucoma, with relatively high prevalence of suspected delayed hypersensitivity reaction (blepharitis). Brinzolamide may be the safer option for the treatment of glaucoma in dogs.