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Pulmonary embolism (PE) is a rather common cardiovascular disorder constituting one of the major manifestations of venous thromboembolism (VTE). It is associated with high mortality and substantial recurrence rates, and its diagnosis may be challenging, especially in patients with respiratory comorbidities. Therefore, providing a prompt and accurate diagnosis for PE through developing highly sensitive and specific diagnostic algorithms would be of paramount importance. There is sound evidence supporting the use of biomarkers to enhance the diagnosis and predict the recurrence risk in patients with PE. Therefore, several novel biomarkers, such as factor VIII, Ischemia Modified Albumin, and fibrinogen, as well as several MicroRNAs and microparticles, have been investigated for the diagnosis of this clinical entity. The present review targets to comprehensively present the literature regarding the novel diagnostic biomarkers for PE, as well as to discuss the evidence for their use in daily routine. CA extern