OBJECTIVES: High-dose statin therapy has been reported to be associated with increased risk of side effects, which may reduce treatment adherence and impact cardiovascular (CV) outcomes. This study assessed association between initial statin dose and treatment adherence and persistence and its impact on CV outcomes in the overall and sub-population with prior CV events. METHODS: An observational, retrospective study was conducted in a UK linked database (CPRD) comprising primary care, secondary care (Hospital Episode Statistics), and mortality data. Study cohort was statin-naïve patients initially prescribed statin therapy from January 2003–July 2011, and registered within the practice for ≥1 year preceding statin initiation. High-dose was defined as simvastatin 80mg, fluvastatin 80mg, atorvastatin>20mg, rosuvastatin>10mg. Adjusted Cox regression models were used to predict factors associated with discontinuation and CV event risk. RESULTS: Only 2% (4,744/218,808) of patients started on a high-dose statin; 4,399/4,744, (93%) on atorvastatin, a third taking atorvastatin 80mg.  Adherence was high based on prescribed medication possession ratio for high- (0.96, SD:0.08) and low-dose (0.95, SD:0.10) initiation. Initial dose was not a predictor of discontinuation in the overall population (HR:0.96 95%CI:0.91-1.02), but in patients with CV history, high-dose initiation was associated with lower discontinuation risk (HR:0.87 95%CI 0.78-0.96). In the overall population increased CV event rates were associated with initiation of high-dose statin (OR:2.07 95%CI:1.78-2.41), greater Framingham risk (OR:1.50 95%CI 1.44-1.56), prior unstable angina  (OR:3.06 95%CI:2.53-3.71), heart failure (OR:2.73  95%CI:2.13-3.51), and myocardial infarction (MI) (OR:4.29 95%CI:3.56-5.17). In the CV sub-group, only prior MI was associated with increased CV event risk (OR:1.26 95%CI:1.03-1.55). CONCLUSIONS: Initial high-dose statin was not associated with lower adherence or persistence; among patients with CV history, risk of discontinuation was significantly lower. The association of initial high-dose statin treatment with higher CV event rates may be due to background risk factors leading to use of high-dose statin.