BACKGROUND Patients undergoing total hip or total knee arthroplasty have risks that include venous thromboembolism. The American Academy of Orthopaedic Surgeons has promulgated guidelines for the preoperative assessment of patients with the primary objective of preventing pulmonary embolism. We aimed to evaluate and establish the utility of the first-generation American Academy of Orthopaedic Surgeons guidelines for the prophylaxis of venous thromboembolism in patients undergoing total joint arthroplasty at a single institution. METHODS A prospective analysis of 3289 consecutive patients managed with total hip or total knee arthroplasty at the Connecticut Joint Replacement Institute between June 1, 2009, and April 30, 2011, was conducted. Data on age, sex, body mass index, American Society of Anesthesiologists classification, and a personal or family history of blood clots requiring long-term warfarin use were analyzed, as were data on a personal history of a malignant tumor, a bleeding disorder, gastrointestinal bleeding, or a hemorrhagic cerebrovascular accident. All patients were managed prophylactically with a specific algorithm based on the American Academy of Orthopaedic Surgeons guidelines. All of the patients were mobilized on postoperative day one, and pneumatic foot-pump compression was used for the duration of the hospitalization. RESULTS Thirty-six major venous thromboembolic events were documented with Doppler ultrasound or computed tomography angiography, for a ninety-day incidence of 1.1% (95% confidence interval, 0.8% to 1.5%). A personal history of blood clots was significantly associated with a blood clot in the proximal part of the thigh or a pulmonary embolism, but a family history of blood clots and a personal history of a malignant tumor did not show a significant relationship with venous thromboembolism. The ninety-day incidence of venous thromboembolism was significantly different between total hip arthroplasty patients (0.56%; 95% confidence interval, 0.30% to 1.15%) and total knee arthroplasty patients (1.46%; 95% confidence interval, 1.01% to 2.10%). The risk was greater in high-risk total knee arthroplasty patients compared with high-risk total hip arthroplasty patients despite comparable prophylaxis with enoxaparin sodium for twenty-eight days. CONCLUSIONS The prospective use of the first-generation American Academy of Orthopaedic Surgeons guidelines resulted in a low incidence of clinically important thromboembolic events in total hip and total knee arthroplasty patients. When properly used in these patients, the guidelines to minimize adverse outcomes are executable and effective. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.