This study was designed to compare timolol maleate ophthalmic gel-forming solution 0.5% (timolol gel) once daily with timolol maleate ophthalmic solution 0.5% (timolol solution) twice daily with respect to patient preference, intraocular pressure (IOP)-lowering effect, and tolerability. A total of 202 patients with ocular hypertension or open-angle glaucoma and an IOP > or = 22 mm Hg were enrolled in this 12-week, randomized, observer-masked, two-period crossover study. Significantly more patients preferred timolol gel to timolol solution (P < 0.001). Ninety-two percent of patients preferring timolol gel strongly agreed or agreed that once-daily dosing was a reason for their preference. Those who preferred timolol solution did so because of fewer side effects. The mean IOP-lowering effects of the 2 treatments were similar at both morning trough and peak time points. The incidence of drug-related adverse experiences was similar (timolol gel 11.4% vs timolol solution 10.9%). Because both treatments were well tolerated and effective in lowering IOP, timolol gel, with its once-daily dosing regimen, should be considered in patients who are candidates for therapy with an ophthalmic beta-blocking agent.