Venous thromboembolism (VTE) is a major cause of death and disability throughout the world. Evidenced-based guidelines and performance measures aimed at prevention of VTE have existed for over a decade, yet VTE occurrence rate appears to be increasing. This increase may, in part, be due to more aggressive surveillance; however, noncompliance with guideline recommendations for prophylaxis is a concern. Several barriers have been identified as contributing to lack of guideline adherence including lack of supportive systems, lack of individual responsibility for implementation, lack of acceptance, perceived lack of need in some clinical areas, no oversight or incentives, and conflicting guideline recommendations. Distribution of guidelines to healthcare providers does not result in increased guideline adherence. Applying multiple process improvement strategies appears to increase guideline utilization and may help achieve improved patient outcomes and higher performance measures.