Objective. To investigate the clinical study of intravitreal injection of anti-VEGF drugs combined with intravitreal injection of tretinoin for the treatment of Coats disease. Methods. The medical records of 90 patients (120 eyes) with Coats disease admitted to our hospital from April 2010 to June 2021 were selected as retrospective study subjects and divided into control and treatment groups according to the numerical table method. There were 45 cases and 60 eyes in each group. Among them, intravitreal tretinoin drug was injected into the control group, and anti-VEGF drug was injected into the vitreous sclera of the treatment group on the basis of the control group. Results. Before treatment, the differences in visual acuity changes between the two groups were not statistically significant ( P > 0.05 ). After treatment, the light perception, manipulation, and indexes of both groups were significantly improved, and the treatment group was significantly better than the control group. This difference was statistically significant ( P < 0.05 ) for statistical study comparison. The effective rate of 95.56% in the treatment group was significantly higher than that of 86.67% in the control group, and the complication rate was significantly lower than that of the control group, with statistically significant differences ( P < 0.05 ). Conclusion. Intravitreal injection of anti-VEGF drugs combined with tretinoin injection can significantly improve the clinical efficacy of patients with Coats disease and improve visual acuity and central retinal thickness, which has certain reference value for the clinical treatment of Coats disease.