Background: The recent cholesterol guideline recommends high-intensity statins in cardiovascular disease (CVD) patients. High-intensity statins are associated with more frequent side effects. Therefore, it may be of concern that these recommendations might reduce statin adherence. Hypothesis: High-intensity statins are associated with lower adherence compared with low- to moderate-intensity statins. Methods: In a national database of 972 532 CVD patients from the Veterans Health Administration, we identified patients receiving statins between October 1, 2010, and September 30, 2011. We assessed statin adherence by calculating proportion of days covered (PDC) and determined whether high-intensity statin therapy was independently associated with a lower PDC. Results: Statins were prescribed in 629 005 (64.7%). Of those, 229 437 (36.5%) received high-intensity statins. Mean PDC (0.87 vs 0.86, P < 0.0001) and patients with PDC ≤0.80 (76.3% vs 74.2%, P < 0.0001) were slightly higher for those receiving low- tomoderate-intensity compared with high-intensity statins. In adjusted analyses, high-intensity statin use was associated with a significant but modest PDC reduction compared with low- to moderate-intensity statin use, whether PDC was assessed as a continuous (β-coefficient: -0.008, P < 0.0001) or categorical (PDC ≤0.80 [odds ratio: 0.94, 95% confidence interval: 0.93-0.96]) measure of statin adherence. Conclusions: An approach of high-intensity statin therapy will lead to a significant practice change, as the majority of CVD patients are not on high-intensity therapy. However, this change may be associated with a very modest reduction in statin adherence compared with low- to moderate-intensity therapy that is unlikely to be of clinical significance.