Purpose: The efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) treatment for Coats' disease remains controversial. This study was designed to evaluate the efficacy and safety of anti-VEGF treatment for Coats' disease. Methods: PubMed, Embase, The Cochrane Library, Clinical Trials, CNKI, and WanFang databases were systematically searched for clinical efficacy and safety studies on anti-VEGF treatment for Coats' disease through June 2021. Study selection, data extraction, and quality assessment were independently performed by 2 reviewers. Quality assessments were performed using the Joanna Briggs Institute Critical Appraisal tools and GRADE-CERQual. Results: A total of 1,501 articles were retrieved and reviewed, of which 24 case series involving 378 patients (range: 3-67 patients each with 3-71 eyes) were included in the analysis. No randomized controlled trials, case-controlled studies, or cohort studies were available for analysis. Most patients were male (60.0%-92.9%), aged 1.35-42.3 years, with a median follow-up time ranging from 3 to 63 months. Among the 24 case series, 22 reported changes in the visual acuity (VA) after anti-VEGF treatment and 21 reported safety outcomes. The results showed that VA improved in 73 patients (37.63%), was stable in 89 (45.87%), and worsening VA was observed in 12 cases (6.19%). The most common adverse event was fibrotic changes (n = 35). Systemic complications were not observed. Conclusions: The results of this study indicate that anti-VEGF drugs provide an effective and relatively safe treatment strategy for Coats' disease. However, conducting well-designed, prospective, randomized clinical trials are necessary to confirm our findings.