Abstract Objective To demonstrate that the intraocular pressure (IOP)–reducing effect of latanoprost once daily is at least as good as that of timolol twice daily in patients with chronic angle-closure glaucoma (CACG). Design Randomized, double-masked, multicenter 12-week study. Participants In all, 137 patients with unilateral or bilateral CACG were treated with latanoprost, and 138 were treated with timolol. Methods Patients received either latanoprost (9 pm) and a placebo (9 am) or timolol (both 9 am and 9 pm). Intraocular pressure was measured at 9 am and 5 pm at baseline and weeks 2, 6, and 12. Main outcome measures The difference between groups in daily IOP (average of 9 am and 5 pm measures) reduction was the primary outcome. Secondary outcomes included differences between groups in IOP reductions at 9 am and 5 pm, and in proportions of patients reaching specified daily IOP levels. Results Using repeated measures (analysis of covariance: intent to treat), mean changes from baseline in daily IOP levels during 12 weeks were −8.2 mmHg and −5.2 mmHg for latanoprost- and timolol-treated patients, respectively (difference: −3.0 mmHg [95% confidence interval: −4.0, −2.1], P<0.001). Greater reductions in IOP levels at both 9 am and 5 pm were found in latanoprost-treated patients ( P<0.001 for both), and greater proportions of patients receiving latanoprost reached prespecified target daily IOP levels ( P<0.001 for all 3 target levels tested). Both drugs were well tolerated. Conclusion Latanoprost administered once daily provides significantly greater IOP reduction in CACG patients than does timolol instilled twice daily.