Venous thromboembolism (VTE) presents as deep venous thrombosis (DVT) or pulmonary embolism (PE). VTE is the third most common fatal cardiovascular condition in the United States. Clinical prediction rules such as the Wells' Criteria for DVT, Wells' Criteria for PE, and Pulmonary Embolism Rule-Out Criteria should be used to determine the pretest probability of DVT or PE. The D-dimer assay is used in low-risk patients to rule out DVT and in moderate-risk patients to rule out PE. Compression ultrasonography is the preferred imaging modality to diagnose DVT. PE typically is diagnosed with computed tomographic pulmonary angiography or with ventilation-perfusion scintigraphy if the patient has contraindications to computed tomographic pulmonary angiography. Preferred outpatient therapy for VTE is a direct-acting oral anticoagulant rather than a vitamin K antagonist or low-molecular-weight heparin. Most patients with acute uncomplicated DVT can be treated as outpatients. The Simplified PE Severity Index can guide treatment decisions for patients with PE. Apixaban or rivaroxaban can be used for initial management without the need to bridge with parenteral therapy. Treatment is recommended for 3 to 6 months after initial VTE. Patients with chronic risk factors, a recurrent VTE after primary treatment, or a first unprovoked VTE should be considered for secondary prevention with a direct-acting oral anticoagulant or warfarin after a bleeding-risk assessment.