Venous thromboembolism (VTE) is a highly significant clinical and public health concern in the United States, particularly in the surgical population, where approximately 2 million patients of >30 million operative procedures performed annually in the United States experience postoperative complications. Previous well-documented research has revealed that longstanding national guidelines that call for risk stratification and trimodal VTE prophylaxis, a comprehensive modality incorporating 3 arms of prophylaxis-chemical, mechanical, and early ambulation-suffer from significant levels of nonadherence. The fallout includes a disconcerting magnitude of cases of preventable morbidity and mortality, and exertion of a weighty cost burden on the US health care system. This evidence-based quality improvement project investigated the level of adherence, and the causes of nonadherence, to national guidelines for VTE prophylaxis among total knee replacement patients at a prominent tertiary facility in central Massachusetts. Chief among the findings, analysis of documented data, augmented by data collected from unannounced mechanical prophylaxis adherence audits, identified frontline staff negligence as the principal cause of nonadherence in the mechanical arm. Overall, the project helped to underscore optimal VTE prophylaxis as a synergistic amalgamation of the trimodal methodology's complementary individual component efficacies.