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Spontaneous remission is common in patients with undiagnosed classic fever of unknown origin (FUO). Although identifying reliable predictors of spontaneous remission in such diagnostically challenging cases could improve their management strategies, few studies have assessed such clinical factors. Recently, studies have reported that 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) alone and integrated with computed tomography (PET/CT) were useful in localizing the source of FUO. In this systematic review and meta-analysis, we assessed the association of results of these imaging modalities with spontaneous remission in patients with classic FUO.We searched PubMed and Scopus from inception until June 30, 2018, and studies that evaluated the PET or PET/CT results of ≥10 adult or adolescent patients with classic FUO who were followed up for at least 3 months were included. At least 2 investigators extracted data and rated quality using the QUIPS-2 tool. We used a random-effects meta-analysis to calculate summary risk ratios (RRs) with 95% confidence intervals (CIs).Nine studies of PET/CT results (418 patients) and 4 studies of standalone PET results (128 patients) were eligible. None explicitly specified the incidence of spontaneous remission as the primary or secondary outcomes of interest. The risk of bias was considered high in all studies because patients received subsequent diagnostic workup based on imaging results. Patients with negative PET/CT results were significantly more likely to present with spontaneous regression than those with positive results (summary RR = 5.6; 95% CI: 3.4–9.2; P < .001; I2 = 0%). In contrast, no significant association was found between standalone PET results and spontaneous remission. The random-effects study-level meta-regression found that PET/CT results [relative RR (rRR) = 7.4; 95% CI: 2.5–21.3; P = .002], compared with standalone PET results, and publication year (rRR = 1.2 per 1 year; 95% CI: 1.0–1.3; P = .013) were significantly associated with spontaneous remission.Limited data suggest that undiagnosed classic FUO patients with negative PET/CT results had a high likelihood of spontaneous remission after a series of unsuccessful investigations for fever workup. Prospective studies should validate these results.