This study was aimed to evaluate the prophylactic anti-glaucoma effect of topical 5% betaxolol (BTX) and 2% dorzolamide (DRZ) on the second eye in dogs with unilateral primary angle closure glaucoma (PACG). Medical records of 60 dogs with unilateral PACG who received prophylactic anti-glaucoma eyedrops in the second eye, from 2016 to 2021, were reviewed. The duration of prophylactic effects of BTX only and DRZ after BTX failure was calculated. The prophylactic effects of BTX were maintained on 28/60 (46.7%) eyes until last visit and BTX failure was observed on median 510 (range, 53-1,927) days in 32/60 (53.3%) eyes. After DRZ instillation in BTX failure eyes, the prophylactic effects were extended at median 610 (range, 157-2,270) days in 21/32 (65.6%) eyes. DRZ failure eyes (17/21, 81.0%) eyes required chemical ablation or surgical intervention due to uncontrolled intraocular pressure. The duration of prophylactic effects was decreased with aging (R² = 0.334, p = 0.006). The predominant breeds were Shih-Tzu (41.9%) and American Cocker Spaniel (30.6%) with no significant differences in survival curves (p = 0.210). The average prophylactic effects of BTX persisted more than 1.5 year and could be selected the first prophylactic eye drop in unilateral PACG. Also, early surgical intervention should be considered in prophylactic medications failure cases.