Background: Cytomegalovirus retinitis (CMVR) is the primary cause of AIDS-related blindness and remains a substantial cause of blindness in resource-limited settings. Retinal detachment (RD) occurs in approximately 1/3 of patients with CMV retinitis. There is limited capacity to treat retinal detachment in resource-limited settings, and retinal detachment commonly results in permanent profound vision loss. Prophylactic argon laser demarcation was widely used in the pre-HAART era in high income countries, and we here describe our experience with this safe, low-cost intervention to prevent blindness from CMV retinitis-related retinal detachment in a resource-limited setting, in the current era where effective antiretroviral therapy is available. Methods: A non-randomized retrospective observational cohort study was conducted over 4 years in patients on cART (combined antiretroviral therapy) and with inactive AIDS-related CMVR involving at least 25% of the retina, and who were treated with prophylactic argon laser demarcation (LD). The main outcomes were retinal detachment and loss of vision.Results: In a 45 eyes from 38 patients with inactive CMVR on cART for HIV/AIDS who underwent prophylactic laser demarcation, there were no retinal detachments and no loss of vision.Conclusion: In this series of patients at risk for CMVR-related retinal detachment who were treated with prophylactic laser demarcation, retinal detachment was prevented and visual acuity was maintained. Prophylactic argon laser demarcation is a safe, effective, and a realistically affordable intervention to reduce blindness in patients with AIDS-related CMV retinitis.