The prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia (CBF-AML), including inv(16) and t(8;21) AML, is uncertain. We performed a systematic review and meta-analysis of the effect of KIT mutations on the complete remission (CR) and relapse rates and overall survival (OS) of CBF-AML. PubMed, Embase, Web of Science, and the Cochrane Library were searched and relevant studies were included. Negative effect was indicated on relapse risk of CBF-AML (RR [relative risk], 1.43; 95%CI [confidence interval], 1.20-1.70) and t(8;21) AML (RR, 1.70; 95% CI, 1.31-2.21), not on OS of CBF-AML (RR, 1.09; 95% CI, 0.97-1.23), CR (OR [odds ratio], 0.95; 95% CI, 0.52-1.74), relapse risk (RR, 1.12; 95% CI, 0.90-1.41) or OS (RR, 1.03; 95% CI, 0.90-1.18) of inv(16) AML. Subgroup analysis of t(8,21) AML showed negative effect of KIT mutations on CR (OR, 2.03; 95%CI: 1.02-4.05), relapse risk (RR, 1.89; 95%CI: 1.51-2.37) and OS (RR, 2.26; 95%CI: 1.35-3,78) of non-Caucasians, not on CR (OR, 0.61; 95%CI: 0.19-1.95) or OS (RR, 1.12; 95%CI: 0.90-1.40) of Caucasians. This study indicates KIT mutations in CBF-AML to be included in the initial routine diagnostic workup and stratification system of t(8,21) AML. Prospective large-scale clinical trials are warranted to evaluate these findings.