I-131 therapy is a common treatment modality for adults with Graves' Disease (GD). Utilizing meta-analysis, we examined patient specific factors that predict I-131 therapy failure.Literature search followed PRISMA. Comprehensive Meta-analysis (version 3.0) was used. Mantel-Haenszel test with accompanying risk ratio and confidence intervals evaluated categorical variables. Continuous data was analyzed using inverse variance testing yielding mean difference or standardized mean difference. Decision tree algorithms identified variables of high discriminative performance.4822 collective patients across 18 studies were included. Male sex (RR = 1.23, 95%CI = 1.08-1.41, p = 0.002), I-131 therapy 6 months after GD diagnosis (RR = 2.10, 95%CI = 1.45-3.04, p 0.001) and history of anti-thyroid drugs (RR = 2.05, 95%CI = 1.49-2.81, p 0.001) increased the risk of I-131 therapy failure. Elevated free thyroxine, 24-h radioactive iodine uptake scan ≥60.26% and thyroid volume ≥35.77 mL were also associated with failure.Patient characteristics can predict the likelihood of I-131 therapy failure in GD. Definitive surgical treatment may be a reasonable option for those patients.