Venous thromboembolism (VTE) prophylaxis is recommended for all patients undergoing total hip arthroplasty or total knee arthroplasty. The selection of an appropriate prophylaxis regimen represents a balance between efficacy and safety. To help orthopaedic surgeons select an appropriate VTE prophylaxis regimen for their patients, the American Academy of Orthopaedic Surgeons and the American College of Chest Physicians have developed guidelines. These guidelines do not recommend an optimal regimen, however. Rather, an individualized prophylaxis regimen that balances efficacy and safety is recommended for each patient, based on various risk factors. Because of a paucity of data and a lack of adequately powered head-to-head trials, implementing these guidelines can be challenging for the orthopaedic surgeon. Knowledge of the prophylaxis options and the VTE risk factors is paramount for developing an effective VTE prophylaxis algorithm for the surgeon’s practice.