Study objective: Syncope is one of the most common presentation of patients seen in emergency departments (ED). Risk assessment of syncope is challenging. The San Francisco Syncope Rule is the most widely used risk assessment, but has moderate accuracy. The aim of our study was to investigate blood biomarkers as prognostic factors for adverse outcome. Methods: In this observational study we included consecutive adults presenting with syncope to our ED. Management decisions were left to the discretion of the treating physicians. Patients were monitored for adverse events until discharge and underwent a phone interview 30 days after enrolment. Adverse outcome was defined as recurrent syncope, rehospitalization and death within 30 days. Results: We included 132 adult patients of whom 19 (14%) had an adverse event (recurrent syncope = 3, rehospitalisation = 12, death = 4). No difference in the San Francisco Syncope Rule was found in patients with and without adverse events (SFSR ≥ 1: 37% vs. 39%, p = 0.877). Median levels of ProADM (1.23 vs. 0.81 nmol/l; p = 0.006) and NT-proBNP (454 vs 134ng/l; p = 0.035) were higher and median levels for cholesterol (3.68 vs 4.57 mmol/l; p = 0.008) and prealbumin (0.19 vs0.26 g/l; p = 0.005) were lower in patients with adverse events. Prealbumin (AUC 0.72) and ProADM (AUC 0.70) had the highest prognostic accuracy. Conclusion: Biomarkers predicted poor outcome and might be helpful in the context of a clinical algorithm for an improved triage of syncope patients in the ED.