We performed a systematic review of English-language studies published during the past three decades to investigate the diagnostic performance of serum glial fibrillary acidic protein (GFAP) for the differential diagnosis of acute stroke, including intracerebral hemorrhage (ICH) and cerebral ischemia (CI). QUADAS tools were used to evaluate the quality of the study. Performance characteristics (diagnostic sensitivity, specificity, and other measures of accuracy) were pooled and examined using fixed-effects models. Four studies met the inclusion criteria, and included 109 patients with ICH and 381 patients with CI. The summary estimates for GFAP in the ICH diagnoses had a diagnostic sensitivity of 0.80 (95% confidence interval 0.71-0.88), a specificity of 0.97 (95% confidence interval, 0.94-0.98), and a diagnostic odds ratio (DOR) of 119.55 (95% confidence interval: 51.75-276.19). The area under curve (AUC) and Q value for the sROC curves were 0.97 and 0.92, respectively. Therefore, GFAP showed high diagnostic accuracy for acute stroke differential diagnosis.