Background Dual-energy CT (DECT) shows promising performance in detecting bone marrow edema (BME) associated with vertebral body fractures. However, the optimal technical and image interpretation parameters are not well described. Purpose To conduct a systematic review and meta-analysis to determine the diagnostic performance of DECT in detecting BME associated with vertebral fractures (VFs), using different technical and image interpretation parameters, compared with MRI as the reference standard. Materials and Methods A systematic literature search was performed on July 9, 2020, to identify studies evaluating DECT performance for in vivo detection of vertebral BME. A random-effects model was used to derive estimates of the diagnostic accuracy parameters of DECT. The impact of relevant covariates in technical, image interpretation, and study design parameters on the diagnostic performance of DECT was investigated using subgroup analyses. Results Seventeen studies (with 742 of 2468 vertebrae with BME at MRI) met inclusion criteria. Pooled estimates of sensitivity, specificity, and area under the curve of DECT for vertebral body BME were 89% (95% CI: 84%, 92%), 96% (95% CI: 92%, 98%), and 96% (95% CI: 94%, 97%), respectively. Single-source consecutive scanning showed poor specificity (78%) compared with the dual-source technique (98%, P < .001). Specificity was higher using bone and soft-tissue kernels (98%) compared with using only soft-tissue kernels (90%, P = .001). Qualitative assessment had a better specificity (97%) versus quantitative assessment (90%) of DECT images (P = .01). Experienced readers showed considerably higher specificity (96%) compared with trainees (79%, P = .01). DECT sensitivity improved using a higher difference between low- and high-energy spectra (90% vs 83%, P = .04). Conclusion Given its high specificity, the detection of vertebral bone marrow edema with dual-energy CT (DECT) associated with vertebral fracture may obviate confirmatory MRI in an emergency setting. Technical parameters, such as the dual-source technique, both bone and soft-tissue kernels, and qualitative assessment by experienced readers, can ensure the high specificity of DECT. © RSNA, 2021 Online supplemental material is available for this article.