OBJECTIVES: Fever of unknown origin (FUO) is defined as temperature > 101°F on several occasions duration of fever of more than 3 weeks and failure to reach to diagnosis despite one week of inpatient investigations. This study aimed to perform a systematic review to examine the overall diagnostic performance of FDG-PET/PET CT in identifying the causal source of FUO. METHODS: We searched potentially relevant studies using electronic databases such as Ovid-Medline, Ovid-EMBASE, Cochrane library, KoreaMed, and Kmbase from their inception to May, 2012. Two independent reviewers extracted data using a standardized form. The quality of the selected studies was assessed using QUADAS-2. A bivariate random model was constructed to summarize the sensitivity, specificity and area under the curve (AUC). RESULTS: A total of 15 studies representing 592 patients were eligible for inclusion. Overall, the studies had ‘poor’ methodological quality. Concerns about applicability are rated as ‘low’. AUC of 6 FDG-PET studies was 0.7955, and the pooled diagnostic odds ratio (DOR) was 9.38 (95% CI 1.44-60.91). Pooled sensitivity was 0.859 (95% CI 0.729-0.932), and the pooled specificity was 0.664 (95% CI 0.416-0.845). As the results of meta-regression in accordance with the absence of blinding that causes heterogeneity, pooled specificity was significant difference (blinding 0.816, non-blinding/unclear 0.344, P=0.013). AUC of 9 FDG PET-CT studies was 0.8071, and the pooled DOR was 10.93 (95% CI 4.67-25.57). Pooled sensitivity was 0.838 (95% CI 0.715-0.914), and the pooled specificity was 0.714(95% CI 0.588-0.814). CONCLUSIONS: FDG PET/PET-CT test appeared to have a high sensitivity and a moderate specificity for the detection of the causes of FUO. However, since a limited number of studies are available and included studies were heterogeneous with respect to the aspect of study design, the method of interpretation of test result. More rigorous and larger prospective studies are needed.