Abstract Background: Glaucoma is one of the most important cause of irreversible blindness in the world. Elevated Intraocular Pressure (IOP) remains the main known risk factor for the development and progression of the disease. The main thera-peutic goal is to preserve visual function by reducing the IOP, which is the key modifiable risk factor. Aim of Study: Is to compare the effect and safety of Dorzolamide/Timolol-Fixed Combination (DTFC) and Bri-monidine/Timolol-Fixed Combination (BTFC), on corneal endothelium after 3 months. Patient and Methods: This comparative non-randomized controlled clinical trial study included 57 eyes of 57 patients which was conducted in Damietta Eye Hospital. Their age ranged from 20-70 years old. The study population was divided into two groups: First group receiving DTFC: Included 27 eyes of 27 patients with open angle glaucoma and second group receiving BTFC included 30 eyes of 30 patients with open angle glaucoma. Result: Show that this adjusted difference between group 1 and group 2 through 3 months follow-up had no statistical significance in all variables such as IOP (p=0.172), CCT (p=0.072) and CD (p=0.406). Conclusion: The patients that received two fixed-combination (dorzolamide/timolol) and (brimonidine/timolol) had no statistically significant effect on CCT and ECD after 3 months from using these drugs.