AbstractBackground/introductionIn patients with acute vestibular syndrome (AVS), differentiating between stroke and nonstroke causes is challenging in the emergency department (ED). Correct diagnosis of vertigo etiology is essential for early optimum treatment and disposition.ObjectivesThe aim of this systematic review and meta‐analysis was to summarize the published evidence on the potential of blood biomarkers in the diagnosis and differentiation of peripheral from central causes of AVS.MethodsA literature search was conducted for studies published until January 1, 2023, in PubMed, Ovid Medline, and EMBASE databases analyzing biomarkers for the differentiation between central and peripheral AVS. The Quality Assessment of Diagnostic Accuracy Studies questionnaire 2 was used for quality assessment. Pooled standardized mean difference and 95% confidence intervals were calculated if a biomarker was reported in two or more studies. Heterogeneity among included studies was investigated using the I² metric.ResultsA total of 17 studies with 859 central and 4844 peripheral causes of acute dizziness or vertigo, and analysis of 61 biomarkers were included. The general laboratory markers creatinine, blood urea nitrogen, albumin, C‐reactive protein, glucose, HbA1c, leukocyte counts, and neutrophil counts and the brain‐derived biomarkers copeptin, S100 calcium‐binding protein β (S100β), and neuron‐specific enolase (NSE) significantly differentiated central from peripheral causes of AVS.ConclusionsThis systematic review and meta‐analysis highlights the potential of generalized inflammatory markers and brain‐specific blood protein markers of NSE and S100β as diagnostic biomarkers for central from peripheral differentiation in AVS. These results, as a complement to clinical characteristics, provide guidance for future large‐scale diagnostic research, in this challenging ED patient population.