Objective To compare the therapeutic efficacy and safety of ganciclovir and foscarnet sodium in the treatment of patients with acquired immunodeficiency syndrome (AIDS) complicated with cytomegalovirus retinitis (CMVR). Methods A retrospective analysis was conducted on the clinical data of 82 patients with AIDS complicated with CMVR who were admitted to the Zhengzhou Sixth People""s Hospital between January 2022 and December 2024. According to the different treatment regimens, the patients were divided into the ganciclovir group (n＝42) and the foscarnet sodium group (n＝40). Both groups received standard anti-cytomegalovirus (CMV) therapy and highly active anti-retroviral therapy (HAART). The changes in visual acuity, control of lesions, incidence of adverse reactions and improvement in CD4+ T cell count were compared between the two groups before and after treatment. Results There was no statistically significant difference in the rate of visual acuity improvement between the two groups (P＞0.05), but the ganciclovir group demonstrated a greater improvement in visual acuity (P＜0.05). There was no statistically significant difference in the lesion control rate and the incidence of adverse reactions between the two groups (all P＞0.05). Both groups exhibited a significant increase in CD4+ T cell counts aftertreatment; however, the difference in the magnitude of improvement between the groups was not statistically significant (P＞0.05). Conclusion Ganciclovir and foscarnet sodium have comparable efficacy in the treatment of AIDS complicated with cytomegalovirus retinitis (CMVR), but ganciclovir has a greater advantage in the improvement of visual acuity. In clinical treatment, ganciclovir should be preferred based on the patient""s basic condition to improve the prognosis of visual acuity.