The Ocular Histoplasmosis Study-Krypton Laser is a multicenter controlled clinical trial designed to determine whether krypton red laser photocoagulation is of value in preventing visual acuity loss in eyes with ocular histoplasmosis that have either choroidal neovascularization 1 to 199 micron from the center of the foveal avascular zone (FAZ) or choroidal neovascularization 200 micron or further from the FAZ center with blood and pigment extending within 200 micron of the FAZ center. Patients were assigned to photocoagulation (n = 143) or to observation only (n = 145). Recruitment of patients with such lesions has been stopped because more untreated eyes than treated eyes had experienced severe visual acuity loss. At one year after randomization, 24.8% (31/125) of untreated eyes, in contrast with 6.6% (8/121) of treated eyes, had lost six or more lines of visual acuity; by three years after randomization, the corresponding values were 24.6% (15/61) and 4.6% (3/64). The superiority of treatment was evident at every point in time after six months. There were no subgroups in which there was convincing evidence that treatment was harmful. Follow-up of all patients continues to assess long-term results of treatment.