INTRODUCTION: This study evaluated the use of statin therapy in U.S. Air Force (USAF) aviators with isolated hypercholesterolemia in terms of compliance with clinical practice guidelines (CPGs) and effectiveness in reducing low-density lipoprotein cholesterol (LDL-C) and coronary heart disease (CHD) risk.METHODS: This was a mixed design, 8-yr retrospective study that included 8185 participants with isolated hypercholesterolemia, of which 1458 (17.81%) were prescribed statin monotherapy.RESULTS: Overall agreement between CPG recommendations and patient-clinician decision makers was 0.920 (95% confidence interval: 0.955, 0.959) and 0.891 (95% confidence interval: 0.843, 0.851) per 2002 and 2013 CPGs, respectively. Overall agreement was primarily driven by the negative proportion of specific agreement; positive agreement was moderate for the 2002 CPG and poor for the 2013 CPG. LDL-C levels marginally decreased for all participants except non-CPG-recommended statin users per the 2002 CPG. CHD risk was minimally reduced for all participants per the 2002 CPG with the exception of CPG-recommended statin users, for whom risk increased; CHD risk decreased for CPG-recommended statin users, but increased for non-CPG-recommended statin users per the 2013 CPG. No one statin medication was found to be more clinically effective in reducing LDL-C or CHD risk, regardless of dose intensity.CONCLUSIONS: Aerospace medicine practitioners are following CPG recommendations for statin therapy. Statins provided minimal benefit, however, and CPG recommendations proved irrelevant in reducing LDL-C and CHD risk in this population of Air Force aviators. This result is attributable, in part, to the young age of the study cohort and the short follow-up period.Tvaryanas AP, Mahaney HJ, Schroeder VM, Maupin GM. Statin therapy in low-risk air force aviators with isolated hypercholesterolemia. Aerosp Med Hum Perform. 2017; 88(8):752–759.