Anticoagulants are the treatment of choice for venous thromboembolism (VTE). In the acute phase, the preferable drug is determined by short-term VTE severity assessment, drug half-life in relation to bleeding risk, dosage flexibility, and plausible side-effects. Drug-drug interactions, drug accumulation with impaired kidney function or severe liver failure, thrombocytopenia, and overall bleeding risk must also be taken into consideration. Prediagnostic treatment with anticoagulants may also be considered in patients with low bleeding risk and suspected low-risk VTE in order to safely postpone diagnostic imaging to office hours. Low molecular weight heparins are routinely used as the initial anticoagulant therapy. Unfractionated heparins are natural anticoagulants that potentiate antithrombin. Pharmacological primary prophylaxis is indicated for patients with a moderate or high risk for VTE that outweighs the risk for bleeding complications. Early mobilization with active physiotherapy, lower limb elevation at bedrest, and compression stockings are complementary to pharmacological prophylaxis.