Background: primary open-angle glaucoma  is asymptomatic optic neuropathic ocular disease characterized by enlarging optic disc cupping and visual field loss. World Health Organization estimated in a systemic review that glaucoma is the second commonest cause of blindness worldwide and topical ocular hypotensive medication was effective in delaying the onset of open angle glaucoma in individuals with elevated ocular pressure. Aim of the work: the study aimed to evaluate the safety and pressure-lowering efficacy of travoprost (0.004%) compared to timolol 0.5% and compared to brimonidine tartrate 0.2% as monotherapy in patients with primary open-angle glaucoma Patients and methods: patients were randomized to 3 groups, the first group was received travoprost 0.004%, the second group was received timolol 0.5% and the last group was received brimonidine tartrate 0.2%. This study was carried out in Menoufia University during the period from January 2016 to January 2017. Result: this study included 45 patients who were randomized to 3 groups, the first group received prostaglandins analogue, the second group received beta blockers and the last group received alpha agonists. Collected data indicated that the intraocular pressure–lowering efficacy of travoprost was significantly better compared to timolol and brimonidine at months 3, 6, 9, 12 (P <.001). Conclusion: using primary monotherapy, the intraocular pressure–lowering efficacy of travoprost 0.004% was superior to timolol 5% and superior to brimonidine tartrate 0.2% in patients with primary open-angle glaucoma. Travoprost, timolol and brimonidine reduced intraocular pressure effectively in primary open angle glaucoma.