Purpose To compare the efficacy and safety of topical bimatoprost (LUMIGAN; Allergan, Inc., Irvine, CA) once daily with that of topical combined timolol and dorzolamide (Cosopt; Merck & Co, Inc., Whitehouse Station, NJ) twice daily. Design Prospective, randomized, double-masked, multicenter clinical trial. Participants One hundred seventy-seven patients with a diagnosis of glaucoma or ocular hypertension and inadequate control of intraocular pressure (IOP) after at least 2 weeks of topical timolol maleate 0.5% monotherapy. Methods Patients were randomized to receive bimatoprost 0.03% once daily (n = 90) or combined timolol 0.5% and dorzolamide 2% twice daily (n = 87) over a 3-month period. Main outcome measures Intraocular pressure, the primary end point, was measured at 8 am and 10 am at baseline, week 1, and months 1, 2, and 3, and also at 4 pm and 8 pm at baseline and month 3. Results Bimatoprost provided significantly greater IOP lowering compared with combined timolol and dorzolamide. At the 8 am measurements, bimatoprost lowered mean IOP 6.8 mmHg to 7.6 mmHg from baseline, whereas combined timolol and dorzolamide lowered mean IOP 4.4 to 5.0 mmHg from baseline ( P<0.001). At the last follow-up, patients had better diurnal IOP control with bimatoprost than combined timolol and dorzolamide. At 8 am at the 3-month visit, the percentages of patients achieving IOPs of ≤13 mmHg, ≤14 mmHg, ≤15 mmHg, or ≤16 mmHg were more than twice as high for bimatoprost than for combined timolol and dorzolamide (all P≤0.008). Taste perversion, ocular burning, and stinging with instillation were more common with combined timolol and dorzolamide, whereas conjunctival hyperemia was more common with bimatoprost. Conclusions In individuals with glaucoma or ocular hypertension, uncontrolled on a topical β-blocker alone, bimatoprost lowered IOP more consistently than did combined timolol and dorzolamide.