Purpose: Previous studies have demonstrated that visual function as measured by contrast sensitivity (CS) improves in primary open-angle glaucoma (POAG) patients following beta-blocker therapy and trabeculoplasty. There is evidence that ocular hypotensive agents, such as latanoprost, may provide benefit in terms of improved visual function, despite relatively small differences in the ocular hypotensive effect, when compared to other drugs. The aim of this study was to prospectively compare the effects of latanoprost and timolol maleate in Gelrite on CS. Methods: Twenty (20) POAG patients on a monotherapy treatment regimen of topical beta blockade and with clinically stable intraocular pressure (IOP) were recruited for this single-masked, randomized, crossover study. Subjects were randomized to begin treatment with latanoprost 0.005% once-daily in the evening or timolol maleate 0.5% in Gelrite once-daily in the morning. At the end of a 3-month treatment period, each subject was crossed over to receive the alternative treatment for 3 months. Blood pressure, heart rate, IOP, and CS were assessed at baseline and after 4, 12, 16, and 24 weeks of treatment. Static central contrast sensitivity was evaluated at four spatial frequencies, 3, 6, 12, and 18 cycles/degree. Visual-field sensitivity was evaluated by using a commercially available program. Static threshold visual-field sensitivity was assessed at baseline and after 12 and 24 weeks of treatment. Results: Subjects who were treated for 3 months with latanoprost, after being switched from timolol, experienced an improvement in CS at 3 cpd (P = 0.03). Conversely, subjects who were treated for 3 months with timolol, after being switched from latanoprost, demonstrated a significant loss in CS at 3 cpd (P = 0.04) and at 18 cpd (P = 0.03). Changes in CS occurred without a corresponding change in IOP, since there were no between-group differences (P > 0.05) at the end of each treatment phase. Conclusions: Compared with timolol maleate in Gelrite, latanoprost appears to significantly improve, or at least maintain, central visual function, as measured by CS, at different spatial frequencies in patients with POAG. © 2008 Mary Ann Liebert, Inc.