Purpose: To compare the IOP-lowering efficacy and safety of travoprost (0.0015% and 0.004%) to timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. Methods: In this international, multicenter, double-masked, parallel group study, 573 patients were randomized to travoprost 0.0015%, travoprost 0.004%, dosed QD in the evening (and placebo QD in the morning), or timolol 0.5% dosed BID. IOP was measured at week 2 and at months 1.5, 3, 4.5, 6 and 9, along with an evaluation of safety. The primary efficacy variable was mean IOP at 9 AM, 11 AM and 4 PM for the patient’s worse eye. Results: Travoprost (0.0015% and 0.004%) produced clinically relevant and statistically significant reductions from baseline in mean IOP (p=0.0001). These reductions in mean IOP ranged from 7.1 to 8.3 mmHg for travoprost 0.0015%, 8.0 to 8.9 mmHg for travoprost 0.004%, and from 6.3 to 7.9 mmHg for timolol 0.5%. Average hyperemia scores were none/trace to mild and ranged from 0 to1 on a scale of 0 to 3 for all study groups. Changes in iris pigmentation were observed in approximately 4 to 5% of patients treated with travoprost and none with timolol. There were no serious, related adverse events reported for any treatment group. Conclusions: Travoprost 0.004% is superior to timolol 0.5% in the reduction of IOP in patients with open-angle glaucoma or ocular hypertension when used as primary therapy. Travoprost is safe and well tolerated.