Background Procalcitonin, a precursor hormone of calcitonin, represents a promising marker of bacterial infections. Research Question What is the accuracy of procalcitonin for the diagnosis of sepsis in adult patients in the emergency department (ED)? Study Design and Methods In this this systematic review and meta-analysis, we searched 5 databases (PubMed, Google Scholar, Science Direct, Wiley, and the Cochrane database) from the inception of the Third International Consensus Definitions for Sepsis and Septic Shock diagnostic criteria (January 1, 2016) through December 31, 2024. We included studies that assessed the accuracy of procalcitonin for sepsis in adult patients admitted in the ED. We performed a random-effects meta-analysis, evaluated individual study risk of bias using Quality Assessment of Diagnostic Accuracy Studies 2 criteria and certainty of evidence using Grading of Recommendations, Assessment, Development, and Evaluations methodology. Results We included 11 studies comprising 7,937 patients in the analysis. The pooled sensitivity of procalcitonin for sepsis in patients in the ED was 0.62 (95% CI, 0.60-0.64) and the pooled specificity was 0.80 (95% CI, 0.79-0.81); both were based on low certainty evidence. The pooled positive likelihood ratio was 2.80 (95% CI, 2.20-3.57), the negative likelihood ratio was 0.42 (95% CI, 0.32-0.55), and the pooled diagnostic OR was 6.83 (95% CI, 4.87-9.58). The area under the receiver operating characteristic curve for procalcitonin was 0.77 (95% CI, 0.7281-0.8309). Conclusions Based on pooled analysis, procalcitonin was shown to have reasonable specificity but poor sensitivity for diagnosis of sepsis in patients in the ED with suspected infection. Given that the results are based on low certainty of evidence, further high-quality data in this population are needed. Clinical Trial Registration International Prospective Register of Systematic Reviews; No.: CRD42024618786; URL: https://www.crd.york.ac.uk/prospero/