OBJECTIVES: To develop United States (US) cost model estimates for venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE).  Total US costs were calculated as well as hospital-acquired, “preventable”, and indirect VTE costs.  METHODS:  A literature review was performed to determine VTE incidences, morbidity probabilities, case-fatality rates, and direct medical and indirect costs.  Indirect costs were derived from present value of lifetime earnings (PVLE) due to premature death.  Two decision trees mapping PE and DVT outcomes were developed, and cost models were constructed in Microsoft Excel.  The decision trees first contain primary VTE characteristics and outcomes: hospital- or community-acquired; fatal versus non-fatal; readmission/recurrence versus none; and instant versus non-instant death.  Initially surviving patients are at risk for associated morbidities: minor bleed; major bleed; heparin induced thrombocytopenia; chronic thromboembolic pulmonary hypertension; post-thrombotic syndrome; and resolution or no resolution of symptoms or death.  The average patient’s cost, the sum of each decision tree pathway’s probability-weighted cost, were multiplied by low and high annual PE and DVT incident events to determine total cost ranges.  All costs were adjusted to 2011 US dollars.  Two multi-way sensitivity analyses were conducted: one analysis has higher probabilities and costs; the second introduces long term attack rates (LTAR), pooled incident and recurrent events, into the baseline and first multi-way sensitivity analyses with only low VTE incidences. RESULTS: Annual US total base case (LTAR sensitivity analysis), hospital-acquired, preventable, and indirect VTE costs range from $13.4-27.0 ($15.3-34.3) billion, $8.9-18.0 ($10.2-25.3) billion, $4.5-14.0 ($5.1-12.7) billion, and $4.5-9.8 ($5.6-11.7) billion, respectively.  PE comprises the majority of VTE costs.  Indirect costs due to PVLE represent at least 33% of total VTE costs.  CONCLUSIONS: The United States could avoid substantial costs, morbidity and mortality if effective VTE prophylactic strategies were implemented.  This attainable goal would contribute to important health care reform.