Purpose: To compare latanoprost with the fixed-combination latanoprost-timolol in glaucoma or ocular hypertension patients switched from a combination glaucoma therapy with timolol and another nonprostaglandin medication. Design: Prospective randomized clinical trial. Methods: Glaucoma or ocular hypertension patients receiving a combined treatment of timolol 0.5% and another nonprostaglandin medication (pilocarpine 4% , α -agonist, or a topical carbonic anhydrase inhibitor) underwent a 30- day washout of their medications. A masked observer then measured their intraocular pressure (IOP). The subjects were randomized to either latanoprost or fixed-combination latanoprost-timolol eyedrops to use once daily at 7 am. The IOP was measured again 30 days after the patients started using one of the study drugs by the same examiner at the same time. Main Outcome Measure: Comparison of the study medications’ hypotensive effect. Results: Fifty-three eyes (28 in the latanoprost group and 25 in the latanoprost-timolol group) from 28 patients were included in the study. The IOP reduction was greater in both study groups compared with the previous combination therapy with timolol and another nonprostaglandin medication in millimeters of mercury (7.7± 2.3 vs. 5.5± 2.3, P < 0.001, for the latanoprost group; 8.5± 3.5 vs. 6.3± 2.7, P < 0.001, for the latanoprost-timolol group) and percentage (35.8± 8.2% vs. 25.6± 8.9% , P < 0.001, for the latanoprost group; 38.6± 8.7% vs. 28.6± 9.0% , P < 0.001, for the latanoprost-timolol group). There was no statistical difference between latanoprost and fixed-combination latanoprost-timolol in reducing IOP, in either millimeters of mercury (P=0.3) or percentage (P=0.2). Conclusions: Both latanoprost and fixed-combination latanoprost-timolol may be viable substitutes for timolol and another nonprostaglandin medication in glaucoma or ocular hypertension patients. Purpose: To compare latanoprost with the fixed-combination latanoprost-timolol in glaucoma or ocular hypertension patients switched from a combination glaucoma therapy with timolol and another nonprostaglandin medication. Design: Prospective randomized clinical trial. Methods: Glaucoma or ocular hypertension patients receiving a combined treatment of timolol 0.5% and another nonprostaglandin (pilocarpine 4%, alpha -agonist, or a topical carbonic anhydrase inhibitor) underwent a 30-day washout of their medications. A masked observer then their intraocular pressure (IOP). The subjects were randomized to either latanoprost or fixed-combination latanoprost-timolol eyedrops to use once daily at 7 am. The IOP was measured again 30 days after the patients started using one of the study drugs by the same examiner at the same time. Main Outcome Measure: Comparison of the study medications’ hypotensive effect. Results: Fifty-three eyes (28 in the latanoprost group and 25 in the latanoprost-timolol group from 28 patients were included in the study. The IOP reduction was greater in both study groups compared with the previous combination therapy with timolol and another nonprostaglandin medication in millimeters of mercury (7.7 ± 2.3 vs. 5.5 ± 2.3, P <0.001 for the latanoprost group; 8.5 ± 3.5 vs. 6.3 ± 2.7, P <0.001 for the latanoprost-timolol group) and percentage (35.8 ± 8.2% vs. 25.6 ± 8.9%, P <0.001 for the latanoprost group; 38.6 ± 8.7% vs. 28.6 ± 9.0%, P <0.001 for the latanoprost-timolol group). There was no statistical difference between latanoprost and fixed-combination latanoprost-timolol in reducing IOP, in either millimeters of mercury (P = 0.3) or percentage (P = 0.2). Conclusions: Both latanoprost and fixed-combination latanoprost-timolol may be viable substitutes for timolol and another nonprostaglandin medication in glaucoma or ocular hypertension patients.