Objectives: The 2013 American College of Cardiology (ACC)/ American Heart Association (AHA) cholesterol treatment guideline recommends monitoring percent reduction in low-density lipoprotein cholesterol (LDL-C) among patients initiating statins as an indication of response and adherence. We examined LDL-C reduction and statin adherence among high-risk patients initiating statins in a real-world setting. Study Design: Retrospective cohort study. Methods: The study population included Kaiser Permanente Georgia members (n = 1066) with a history of coronary heart disease or risk equivalent(s) initiating statins in 2011. Percent change in LDL-C was defined using measurements before and 60 to 450 days after statin initiation. Statin adherence was defined by proportion of days covered, categorized as high (=80[%]), intermediate (50[%]-79[%]), and low (<50[%]). Results: Overall, 58.4[%] of patients failed to achieve a =30[%] LDL-C reduction after statin initiation. The prevalences of high, intermediate, and low statin adherence were 41.3[%], 23.2[%], and 35.6[%], respectively. Of patients with high adherence, 42.3[%] did not achieve a =30[%] reduction in LDL-C compared with 54.7[%] and 79.7[%] of those with intermediate and low statin adherence, respectively. After multivariable adjustment, and compared with those with high adherence, the risk ratios for not achieving a =30[%] LDL-C reduction were 1.31 (95[%] CI, 1.13-1.52) and 1.88 (95[%] CI, 1.67-2.11), for those with intermediate and low adherence. Women and African Americans were less likely to have high adherence, whereas having cardiologist visits was associated with high adherence. Conclusions: In a real-world setting, many patients did not achieve a 30[%] or larger LDL-C reduction. These data support the ACC/AHA recommendation to monitor LDL-C response among patients initiating statins.