Venous thromboembolism (VTE) is a major US health problem. However, the total number of US inpatients who are at risk for VTE is unknown. Our objective was to estimate the number of US acute-care hospital inpatients who were at risk for VTE according to criteria established by the Seventh American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic and Thrombolytic Therapy guidelines for VTE prevention. Using the 2003 Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project (HCUP), patient diagnoses and procedures were examined to identify major surgery patients (age ≥ 18 years, length of hospital stay ≥ 2 days) and medical patients (age ≥ 40 years, length of hospital stay ≥ 2 days). ACCP guidelines were used to estimate the number of surgical and medical patients at risk of developing VTE. Of an estimated 38,220,659 discharges in 2003, 7,786,390 (20%) were surgical inpatients; 44% of which were at low risk for VTE, while 15%, 24%, and 17% were at moderate, high, and very high risk for VTE, respectively. Of the remaining 15,161,586 medical patients, 7,742,419 (51%) met ACCP VTE risk criteria. Over 12 million patients, comprising 31% of US hospital discharges in 2003, were at risk of VTE. Given the existence of internationally-accepted evidence-based guidelines for prevention of VTE, research is required to establish if this patient population is receiving recommended VTE prophylaxis. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc.