The purpose of this meta-analysis was to evaluate the utility of positron emission tomography (PET) using fluor-18-deoxyglucose (FDG) to predict the response of rectal cancer to neo-adjuvant therapy. All previously published studies on the role of FDG-PET in predicting the response of rectal cancer to neo-adjuvant therapy were collected. Pooled sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using statistical software. A total of 28 studies, comprising 1,204 patients with rectal cancer, were included in the meta-analysis. Pooled sensitivity, specificity, PPV and NPV for FDG-PET predicting the response to therapy was 78% [95% confidence interval (CI): 75–82%], 66% (95% CI: 62–69%), 70% (95% CI; 66–73%) and 75% (95% CI: 71–0.79%), respectively. The included studies were of a relatively high methodological quality according to the QUADAS (quality assessment of studies of diagnostic accuracy included in systematic reviews) criteria. Based on the subgroup analyses, there was no significant difference between the response index, the standardized uptake value and the visual response score in predicting the therapy response. However, the accuracy of the group that underwent PET scanning during therapy showed significantly higher values (sensitivity 86% and specificity 80%) than the group that was scanned after completion of the therapy. Therefore, FDG-PET is valuable for predicting the response of rectal carcinoma to neo-adjuvant therapy, and early evaluation of response during the therapy may be more promising. However, additional studies using prospective clinical trials will be required to assess the clinical benefit of this strategy.