BACKGROUND: Circulating tumor DNA (ctDNA) offers a novel and minimally invasive approach to the detection of the KRAS oncogene mutation in colorectal cancer. This study was conducted to compare the prognostic value of ctDNA with that of the current gold standard tumor tissue analysis. METHODS: A systematic literature review was conducted to identify relevant articles published from inception to December 27, 2016; the PubMed, Web of Science, Embase, Wanfang and China National Knowledge Infrastructure databases were searched. Pooled specificity, sensitivity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio (DOR) estimates and areas under summary receiver operating characteristic (AUSROC) curves were calculated. We also performed subgroup and sensitivity analyses. RESULTS: Twenty-three studies with 1,715 colorectal cancer patients were included. The overall sensitivity and specificity were 0.75 (95% confidence interval [CI], 0.66-0.82) and 0.98 (CI, 0.95-0.99), respectively. The positive likelihood ratio was 31.8 (95% CI, 14.8-68.3), and the negative likelihood ratio was 0.26 (95% CI, 0.19-0.36). In addition, the AUSROC and DOR were 0.96 (95% CI, 0.93-0.97) and 123 (95% CI, 52-291), respectively. Substantial heterogeneity was observed across studies (I² = 95%, 95% CI, 91-99). None of the subgroups investigated, including those defined by blood sample type, study region, TNM stage, detection site and detection method, could indicate the source of the observed heterogeneity. The results of the sensitivity analysis indicated that the results of our meta-analysis were stable. CONCLUSIONS: Circulating tumor DNA may serve as a viable alternative to tissue analysis for the detection of KRAS mutations in colorectal cancer.