Background: The aim of the present study was to evaluate the clinical efficacy of laser therapy in the prevention of retinal detachment in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis (CMVR). Methods: A total of 96 eyes from 80 patients with AIDS and CMVR who received anticytomegalovirus (anti-CMV) treatment in the ophthalmology and infection centers of Beijing YouAn Hospital, between June 2016 and August 2018 were retrospectively investigated. The patients were randomly divided into a nonlaser group (50 eyes from 43 patients), who were treated with anti-CMV therapy, and a laser group (46 eyes from 37 patients), who were treated with a fundus laser method to close the retinopathy area after commencing the maintenance stage of anti-CMV treatment. Both groups were followed up for 24 months. The safety of laser therapy was observed, and the efficacy of the therapy was determined by evaluating the incidence of retinal detachment. Results: The percentage of retinal detachment in the nonlaser group was 24% compared with 6.5% in the laser group (P=0.018). There was no significant difference between the two groups in the number of CD4+ T cells, the load of human immunodeficiency virus, or the time between the detachment and the end of the induction period. After laser therapy, 39.13% of patients exhibited keratic precipitates (KP), 30.43% had anterior chamber flare (+/-), 50% had anterior chamber flare (+), and 19.57% had anterior chamber flare (++). Intraocular pressure (IOP) increased in 3 eyes within 2 weeks of laser therapy. The retinal pigment reaction was not obvious in 8 eyes. Conclusions: The use of laser therapy in the main maintenance period of anti-CMV treatment can effectively reduce the incidence of retinal detachment in patients with AIDS and CMVR, and the therapy is safe and reliable.