Researchers compare the effects of once-daily and twice-daily administration of a triple-fixed combination of bimatoprost, brimonidine, and timolol, showing that once-daily administration results in a greater decrease in intraocular pressure. This research aimed to evaluate the effectiveness of once-daily versus twice-daily installation of the fixed combination of bimatoprost, timolol, and brimonidine (Triplenex) in patients with primary open-angle glaucoma. Randomized controlled experiment at a government-funded eye hospital. About 30 people diagnosed with primary open-angle glaucoma were tracked for 3 months. A fixed combination of bimatoprost-timolol-brimonidine was administered to the right and left eyes of these individuals either once daily (10:00 PM) or twice daily (10:00 AM; 10:00 PM). The water-drinking test was used to measure intraocular pressure before and after the administration of the fixed combination of bimatoprost, timolol, and brimonidine (basal WDT0), 1 month (WDT1), 2 months (WDT2), and 3 months (WDT3) (Tripletex). Within groups of 2 versus a once-daily regimen, 60 eyes from 30 patients (age: 70.67±9.70 y) were analyzed for the difference in peak intraocular pressure between WDT3 and WDT0. Both groups had comparable baseline clinical features. Peak intraocular pressure was reduced by 6.1±6.1 mm Hg 30.5% in eyes getting 1 drop per day and by 4.3±5.7 mm Hg 21.5% in eyes receiving 2 drops per day between WDT0 and WDT3 (P=0.023). The once-daily group also had a greater reduction in peak intraocular pressure (5.90±6.03 vs. 4.46±4.28 mm Hg, P=0.006) than the twice-daily group when all WDT was taken into account. Once-daily administration of a fixed combination of bimatoprost (0.01%), brimonidine tartrate (0.15%), and timolol maleate (0.5%) is more effective than twice-daily administration in lowering peak intraocular pressure as evaluated by the WDT.