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To investigate the efficacy and safety of selective laser trabeculoplasty as an initial treatment for newly diagnosed open-angle glaucoma, and its role as adjunctive therapy.A prospective multicenter nonrandomized clinical trial was performed. Patients with newly diagnosed open-angle glaucoma or ocular hypertension were assigned to the primary (selective laser trabeculoplasty) treatment group or the control (latanoprost) group according to patient choice. Both groups were followed up at 1, 3, 6, and 12 months. A secondary treatment group was also included to study the efficacy of selective laser trabeculoplasty for patients intolerant of medical therapy or in whom such therapy was unsuccessful, with or without a history of previous argon laser trabeculoplasty.One hundred eyes (61 patients) were enrolled, 74 in the primary treatment group and 26 in the control group. The average absolute and percent reductions in intraocular pressure for the primary treatment group were 8.3 mm Hg or 31.0%, compared with 7.7 mm Hg or 30.6% for the control group (P=0.208 and P=0.879). The responder rates (20% pressure reduction) were 83% and 84% for the primary and control groups, respectively. There were no differences in intraocular pressure lowering with selective laser trabeculoplasty on the basis of angle pigmentation. A modest contralateral effect was observed in the untreated fellow eyes of patients undergoing selective laser trabeculoplasty.Selective laser trabeculoplasty was found to be equally efficacious as latanoprost in reducing intraocular pressure in newly diagnosed open-angle glaucoma and ocular hypertension over 12 months, independent of angle pigmentation. Nonsteroidal antiinflammatory therapy had similar efficacy to steroids after laser therapy. These findings support the consideration of selective laser trabeculoplasty as a first-line treatment for newly diagnosed open-angle glaucoma or ocular hypertension.