Background: Many hospitalized medically ill patients are at risk of VTE, during admission and after discharge. Risk factors include prior VTE, older age, immobility, obesity, heart or respiratory failure, and cancer. ACCP guidelines recommend use of low-molecular weight heparin (LMWH) or unfractionated heparin (UFH), and mechanical prophylaxis otherwise, in high-risk patients. VTE prophylaxis may be underutilized, however. Methods: Using a database linking admission records from >150 US hospitals to health insurance claims, we identified all persons, aged >=40 years, hospitalized from 2003 to 2008 and at high risk of VTE (based on ACCP guidelines). We excluded patients who: (1) underwent surgery; (2) were hospitalized in prior 30 days; (3) were treated for VTE in prior 30 days; (4) had hypercoagulability at admission; and (5) received LMWH, UFH, or fondaparinux (FOND) at therapeutic dosages on hospital day 1 or 2. We examined use of VTE prophylaxis during hospital admission and post-discharge. Results: We identified 35,606 patients who met all study entry criteria. Mean age was 67 years. Only 17.9% of study subjects received in-hospital VTE prophylaxis, most frequently LMWH (10.1%), intermittent pneumatic compression (4.5%), warfarin (2.9%), and/or stockings (2.0%). Prophylaxis use exceeded 25% only in patients with history (>30 days) of VTE and those admitted from nursing homes. Very few patients (1.7%) received post-discharge VTE prophylaxis; use was limited to LMWH. While there were several significant predictors of VTE prophylaxis (nursing home admission [odds ratio, 2.15; 95% confidence interval 1.91-2.42], central venous catheter placement [1.76; 1.60-1.94], ischemic stroke [1.68; 1.54-1.84] obesity [1.58; 1.47-1.70], and prior VTE [1.57; 1.24-1.99]), model discrimination was relatively poor (c statistic = 0.61). Conclusion: VTE prophylaxis is under-utilized in high-risk hospitalized medically ill patients, during initial admission and following hospital discharge.