Objective: To compare clinical efficacy and tolerability of the fixed combination of travoprost/timolol and brinzolamide/brimonidine/timolol in treatment of patients with primary open-angle glaucoma and ocular hypertension. Methods: A total of 147 patients that 270 eyes with primary glaucoma and ocular hypertension which single-drug therapy had no significant effect were chosen for the study in First Hospital of Yulin from January 2013 to June 2015. Patients were divided randomly travoprost/timolol fixed combination treatment group (group A: 75 cases, 138 eyes) and brinzolamide /brimonidine/timolol fixed combination treatment group (group B: 72 cases, 132 eyes). The intraocular pressure (IOP) at time points of 1, 3, or 6 months, ocular surface disease index (OSDI) at time points of 3, 6 months and adverse events occurred in the two groups during the treatment process were compared. Results: There was no difference in IOP between the two groups after treatment for one month (19.21±1.71 vs 19.16±1.75; P>0.05), but the IOP in group A at 8:00 am (15.11±1.37 vs 16.88±1.49; 14.81±1.29 vs 16.15±1.36) or 10:00 am (14.53±1.26 vs 15.39±1.33; 13.79±1.15 vs 15.54±1.36) was significantly lower than group B after treatment for 3 and 6 months (all P<0.05). The OSDI in group A were significantly lower than group B after treatment for 3 (15.42±3.61 vs 16.75±3.72) and 6 months (15.63±3.79 vs 16.99±3.88), the difference was statistically significant (all P<0.05). The adverse events occurred in two groups were significantly different (25.33% vs 44.00%); group A was totally lower than B, the difference was statistically different (P<0.05). Conclusion: The clinical efficacy and tolerability of treatment of primary open-angle glaucoma or ocular hypertension using fixed combination of travoprost/timolol are better than fixed combination treatment of brinzolamide/brimonidine/timolol, and worthy for clinical use.