OBJECTIVES: This study reviewed and summarized US studies describing adherence, persistence, and compliance to lipid lowering therapy (LLT), and factors that influence adherence and persistence. METHODS: A systematic literature review using PubMed, MEDLINE, and EMBASE databases identified US studies that enrolled adults on LLT published since 2004.  Eligible studies had primary data on adherence, persistence, and/or compliance (all definitions for these terms were included), such as medication possession ratio (MPR), proportion of days covered (PDC), time to discontinuation, percentage discontinued, etc.  Results were stratified by study type and further by methods.  Patients could receive any LLT for primary or secondary prevention.  LLTs included statins, ezetimibe, fibrates, niacin, or resins (generic or branded, combination therapies also included).  Data were summarized in evidence tables, and descriptive analysis was performed. RESULTS: A total of 72 full text articles and 28 conference abstracts were identified. Twenty-three studies reported general medication adherence, persistence, and/or compliance, and 77 studies also examined possible predictors of adherence, persistence, and compliance.  Reported 6-month adherence ranged from 60%–83% and 1-year adherence was 43%–79% for statins. One-year statin discontinuation rates were 25%–50% depending on the definition of gap days applied (range 7–180 days). Primary non-adherence (prescriptions written but never filled) was reported at 18%. Results for other LLTs (N=5) generally covered niacin which reported lower adherence rates compared to statins.  While adherence, persistence, and compliance are multifactorial issues, most studies suggested higher adherence among subjects receiving LLT for secondary prevention as compared to primary prevention, and lower adherence and persistence with higher copayment. CONCLUSIONS: Adherence, persistence, and compliance to LLT were suboptimal.  Factors associated with poor adherence included higher copay and no prior cardiovascular events.  These findings provide important implications for patients, physicians and payers, supporting development of individualized plans to improve use of LLTs.