Objectives: To evaluate panretinal photocoagulation for ischemic central vein occlusion and macular grid-pattern photocoagulation for macular edema with reduced visual acuity due to central vein occlusion and to further define the natural history of central vein occlusion. Design: A multicenter randomized controlled clinical trial supported by the National Eye Institute, Bethesda, Md. Patients: A total of 728 eyes from 725 patients were entered into one or more of four study groups: perfused, nonperfused, indeterminate perfusion, and macular edema. Results: Follow-up of study patients is still in progress and no results are available for the randomized groups (nonperfused and macular edema). Thirty-eight (83%) of 46 evaluable eyes in the indeterminate group eventually demonstrated at least 10 disc areas of nonperfusion (28 eyes) or developed iris and/or angle neovascularization before retinal status could be determined (10 eyes). Four-month follow-up information is available for 522 of the 547 eyes in the perfused group. Thirty of these 522 eyes demonstrated iris and/or angle neovascularization at or before the 4-month follow-up visit. An additional 51 eyes had developed evidence of at least 10 disc areas of nonperfusion by the time of the 4-month visit. Conclusions: These findings confirm the importance of frequent follow-up examinations, including undilated slit-lamp examination of the iris, and gonioscopy in the management of all patients with recent onset of central vein occlusion.