BACKGROUND To compare the intraocular pressure (IOP) lowering effect, tolerability, and patient-reported measures of the dorzolamide/timolol fixed combination and the concomitant administration of brimonidine and timolol after 3 months. METHODS Four hundred ninety-two patients with ocular hypertension, primary open-angle glaucoma, exfoliative glaucoma, or pigmentary glaucoma participated in this randomized, observer-masked, multicenter study. Following 3 weeks of timolol monotherapy, patients with a peak IOP of > or = 2 mm Hg were randomized to receive either fixed combination dorzolamide/timolol twice daily or concomitant brimonidine plus timolol twice daily for 3 months. The IOP-lowering effects at peak and trough, tolerability, and patient-reported convenience and satisfaction were measured at months 1 and 3. RESULTS At month 3 peak, the dorzolamide/timolol group had an adjusted mean (SE) change from baseline IOP of -4.30 (0.24) mm Hg versus -5.27 (0.23) mm Hg in the brimonidine-plus-timolol group, with a treatment difference of 0.97 mm Hg (95% CI: 0.40, 1.53). At the month 3 trough timepoint and both month 1 timepoints, the 95% CIs of the treatment differences were within the prespecified comparability boundary of +/- 1.5 mm Hg. The incidence of drug-related adverse experiences was similar between treatment groups. Patient-reported assessments of convenience and satisfaction showed no statistically significant differences between treatment groups. CONCLUSIONS The IOP-lowering effect of the dorzolamide/timolol fixed combination and concomitant brimonidine plus timolol were comparable at 3 of the 4 timepoints measured. Patient-reported measures and the incidence of adverse experiences in both treatment groups were similar.