Objective: To investigate whether statin adherence (defined as proportion days covered, PDC) is associated with LDL-c response in statin initiators on standard and low starting doses of statins, and to detect a possible interaction with sex. Methods: An inception cohort study was conducted using the PharmLines Initiative, a linkage between the Lifelines Cohort Study and the University of Groningen’s IADB.nl (prescription database). First-time statin users were followed from baseline to follow-up measurement. We matched participants (1:1) between the standard-dose and the low-dose group of statin users on the duration of follow-up. Multiple linear regression analysis was used to model the association. Results: In univariate analysis, PDC was significantly associated with LDL-c response similarly (slope = −0.021), in both the standard-dose group (N = 115, p <.001) and the low-dose group (N = 115, p =.003). In the standard-dose group, the same level of PDC appeared to be significantly associated with a greater LDL-c level reduction in women (slope = −0.027, N = 48, p <.001) than in men (slope = −0.017, N = 67, p <.001). Meanwhile, in the low-dose group, the reduction of LDL-c level from baseline seemed to be greater in men (slope = −0.023, N = 56, p <.001) than in women (slope = −0.020, N = 59, p <.001) for the same level of PDC. In multiple regression analysis, the significant association between PDC and LDL-c with a similar pattern to the univariate result was maintained only in the standard-dose group. Conclusions: Adherence is significantly associated with LDL-c response to statins at follow-up. Sex appears to significantly modify this association. At a similar adherence level, women seem to experience a better LDL-c response to standard-dose statins compared to men in a real-world setting.