Despite clinical trial evidence supporting the use of antiplatelets, angiotensin-converting enzyme inhibitors, and statins for cardiovascular risk reduction in high-risk patients, use of such therapies in real-world outpatients in the prospective Vascular Protection Registry and the Guidelines Oriented Approach to Lipid Lowering Registry was suboptimal (78%, 55%, and 75%, respectively). The most frequent reason physicians cited for nonprescription of statins (33%) was that patients were not high risk enough and/or current guidelines did not support statin use. In conclusion, outpatients at high cardiovascular risk continue to be undertreated as a result of a combination of physician underestimation of cardiovascular risk (knowledge gap) and barriers to implementation of evidence-based therapy (practice gap).