Patients hospitalized with acute medical illness have an elevated risk of venous thromboembolism (VTE). American College of Chest Physicians guidelines list various chronic illnesses, sepsis, advanced age, history of VTE, and immobility as risk factors and recommend prophylactic anticoagulation using fondaparinux, low–molecular weight heparin, or low-dose unfractionated heparin. The objectives of this study were to examine pharmacological prophylaxis against VTE among hospitalized medically ill patients and to assess demographic and clinical correlates related to VTE prophylaxis. A retrospective (1999–2010) electronic medical records study included patients aged 40 years and older hospitalized for at least 3 days, with significant medical illness or with a VTE hospitalization 30–365 days before admission. Each patient's first qualifying hospitalization was analyzed. Exclusions were if VTE treatment was started within 1 day of admission, or if warfarin (and not heparin or enoxaparin) was used. Prophylaxis was defined if the first inpatient dose of subcutaneous heparin or enoxaparin was at prophylaxis levels (lower than treatment levels). Multivariable logistic regression was used to examine factors associated with VTE prophylaxis. Among 12,980 patients, 22.1% received prophylaxis (11.8% with enoxaparin, 10.3% with heparin). VTE prophylaxis was positively associated with year of hospitalization, subcutaneous heparin in the month before admission, aspirin, self-pay status, age, and sepsis. VTE prophylaxis was negatively associated with smoking, alcohol, warfarin in the past 30 days, and primary diagnoses of stroke, infectious disease, or inflammatory bowel disease. Pharmacological VTE prophylaxis has increased significantly over the past 12 years but is still largely underused in patients hospitalized with acute medical illness. Multiple demographic, behavioral, and clinical factors are associated with inpatient VTE prophylaxis.