The purpose of this study was to evaluate differences in efficacy and safety of latanoprost as monotherapy compared to adjunctive therapy in primary open-angle glaucoma. We reviewed records of 527 patients who were treated with latanoprost as mono- or adjunctive therapy to reduce the intraocular pressure. Each patient was treated at least three months unless they were discontinued due to an adverse event or lack of efficacy. In the monotherapy group (n=49) baseline intraocular pressure of 23.6+/-5.2 mm Hg fell to 18.4+/-4.3 mm Hg after 4.4+/-2.0 months of follow-up; in the adjunctive therapy group (n=39) baseline intraocular pressure of 21.8+/-5.7 mm Hg fell to 16.7+/-4.6 mm Hg following 4.3+/-1.8 months of therapy which was a similar change from baseline for both groups (P > 0.9). No differences were noted in the class or number of medicines to which latanoprost could be added including: beta-blockers, alpha-agonists and topical carbonic anhydrase inhibitors. The reasons for failure with monotherapy were mostly adverse events (10/15 patients) and with adjunctive therapy lack of efficacy (14/16 patients). Latanoprost is similarly effective as monotherapy and as an adjunctive agent in reducing the intraocular pressure. Latanoprost can be added successfully to a variety of classes of glaucoma medicines used commonly as adjunctive therapy.