Pulmonary embolism (PE) is one of the two forms of venous thromboembolic disease. PE is the most dangerous and fatal form of the disease because if it stays undiagnosed and untreatable, can lead to death. Its appearance is about 120 cases in 100.000 persons. Its presence is associated with hereditary and acquired risk factors. The therapy is the anticoagulants. The primary prevention of pulmonary embolism is based on the recognition of risk factors that, in combination with the estimated thromboembolic risk, results in the early initiation of prophylaxis, which is either pharmaceutical or mechanical, or both. This review analyses current trials in medical patients and especially in critically ill patients. The main patients’ categories that the primary prevention is needed are patients with stroke, hospitalized in intensive care units and those with infections and reduced mobility (including COVID-19 patients). The results demonstrate superiority in the use of heparin (unfractionated and low molecular weight), while the use of direct oral anticoagulants (DOACs) is indicated only in patients that can take oral medicine and mainly in the long- term prevention after discharge. The mechanical prophylactic means are used in combination with the pharmacological means or alone, as monotherapy (favours intermittent pneumatic compression), only in cases of restricted contraindication of pharmacological measures.