OBJECTIVE To compare the efficacy and tolerability of a once daily evening dose of the latanoprost/timolol fixed combination (LTFC) with that of a once-daily evening dose of the bimatoprost/timolol fixed combination (BTFC) in patients with open-angle glaucoma with elevated intraocular pressure (IOP) insufficiently responsive to monotherapy with prostaglandin analogues/prostamides. METHODS Prospective, randomized, evaluator masked, single-center study. METHODS 36 patients with a diagnosis of open-angle glaucoma, with or without pseudoexfoliation, and inadequate control of IOP, insufficiently responsive to monotherapy with prostaglandin analogues/prostamides. METHODS The primary end-points were the change in IOP at 9:00 am from baseline to week 4, and the difference between treatment groups in the mean diurnal IOP reduction from baseline to week 4. RESULTS BTFC provided significantly greater mean diurnal IOP reduction [mean (standard deviation)] 2.8 (0.9) mmHg, compared with LTFC 2.1 (0.6) mmHg, p = 0.0214. Both treatments significantly reduced the IOP from baseline at each IOP time-point measured, p < 0.0001, and for the mean diurnal IOP; p = 0.0049 for the LTFC, and p < 0.0001 for the BTFC. There were no significant differences in average hyperemia scores among groups, 1.25 (0.5) vs. 1.62 (0.69), p = 0.3835, for the LTFC and the BTFC, respectively. CONCLUSIONS The results of this study showed a significantly higher IOP-lowering effect of a once-daily evening dose of the BTFC compared to that of a once-daily evening administration of the LTFC.