Purpose: To systematically review the accuracy of fluorine 18 ((18) F) fluorodeoxyglucose (FDG) positron emission tomography (PET) in the prediction of tumor response to neoadjuvant therapy in patients with esophageal cancer. Materials and Methods: The MEDLINE and EMBASE databases were systematically searched for relevant studies. Methodologic quality of the included studies was assessed. Sensitivities and specificities of F-18 FDG PET in individual studies were calculated and underwent meta-analysis with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. A chi(2) test was performed to test for heterogeneity (defined as P <.10). Potential sources for heterogeneity were explored by assessing whether certain covariates significantly (P <.05) influenced the relative diagnostic odds ratio. Results: Twenty reports, comprising a total of 849 patients with esophageal cancer, were included. Overall, the studies were of moderate methodologic quality. Sensitivity and specificity of F-18 FDG PET ranged from 33% to 100% and from 30% to 100%, respectively, with pooled estimates of 67% (95% confi dence interval: 62%, 72%) and 68% ( 95% confi dence interval: 64%, 73%), respectively. The area under the sROC curve was 0.7815. There was significant heterogeneity in both the sensitivity and specificity of the included studies (P <.0001). Spearman rho between the logit of sensitivity and the logit of 1-specificity was 0.086 (P = .719), which suggested that there was no threshold effect. Studies performed outside of the United States and studies of higher methodologic quality yielded significantly higher overall accuracy. Conclusion: On the basis of current evidence, 18 F FDG PET should not yet be used in routine clinical practice to guide neoadjuvant therapy decisions in patients with esophageal cancer.