We performed a meta-analysis to compare F-FDG-PET and F-FDG-PET/CT for the diagnostic performance in thyroid nodules with indeterminate cytology by Bethesda classification. PubMed and Embase databases were searched for eligible studies from the earliest available date of indexing through September 2019. Only studies with clearly stated histopathology confirmation were included. Publication bias was assessed by Deeks funnel plot. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value, and diagnostic odds ratio was determined by random-effect analysis, respectively. All diagnostic estimate indexes were determined separately for PET alone and PET/CT and were compared pair-wisely using Z-test. We included 214 patients from five PET alone studies and 420 patients from 8 PET/CT studies in this meta-analysis. The range of the prevalence of malignancy was 11% to 27% for PET alone studies (Median, 20%) and 4% to 50% for PET/CT studies (Median, 24%). The sensitivity (0.95 vs 0.73, P < .01), negative likelihood ratio (0.20 vs 0.53, P = .04) and negative predictive value (0.99 vs 0.91, P < .01) of PET alone are significantly better than those of PET/CT. For PET/CT, Fagan nomogram indicated that when the pre-test probability was set at 24%, the negative post-test probability could decrease to 12%. This meta-analysis reveals that in evaluating thyroid nodules with indeterminate cytology by Bethesda classification, the rule-out performance of F-FDG-PET is significantly better than F-FDG-PET/CT, although the latter represents a more objective and accurate technique. We hypothesize that the lack of precise localization of suspicious FDG uptake in the neck region may have contributed to this overvaluation for PET alone studies, and advocate that future studies be performed with PET/CT rather than PET alone to avoid misinterpretation and overvaluation in this scenario.