BACKGROUND: In the Emergency Department, lactate measurement is a useful tool to risk-stratify critically ill patients. However, it is unclear whether arterial or peripheral venous lactate levels can be used interchangeably for this purpose. In this systematic review, we provide an overview of studies investigating the agreement between arterial and peripheral venous lactate levels in the Emergency Department. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials/Wiley, Web of Science/Clarivate Analytics, and references of selected articles were assessed for all studies comparing arterial and peripheral venous lactate levels in adult patients in the emergency department. Two reviewers independently screened all potentially relevant titles and abstracts for eligibility using a standardized data-worksheet. RESULTS: Nine studies were included. Peripheral venous lactate levels tend to be higher than arterial lactate levels with mean differences ranging from 0.18 mmol/l to 1.06 mmol/l. Importantly, poorer agreement occurs in hyperlactatemia. At a cut-of level of 1.6 mmol/l, peripheral venous lactate can rule out arterial hyperlactatemia with a sensitivity between 94% and 100%. At a cut off value of 2 mmol/l, sensitivities of 97% and 100% were found. CONCLUSION: Agreement between arterial and peripheral venous lactate is poor in hyperlactatemia, making peripheral venous lactate an unreliable parameter to use interchangeably in the ED. In clinical practice, peripheral venous lactate can be used as a screening tool to rule out arterial hyperlactatemia at a cut-off value of 2 mmol/l. However, hyperlactatemia should be confirmed using arterial sampling in case of a peripheral venous lactate level > 2 mmol/l.