Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Servier. Background/Introduction One of the most effective strategies for cardiovascular (CV) disease prevention is lipid level control. To achieve this control, a satisfactory level of adherence to effective lipid-lowering medications is required. Purpose To evaluate and compare medication adherence and plasma levels of low-density lipoprotein cholesterol (LDL-C) among 2 cohorts of patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free (FC) or single-pill combination (SPC), in an Italian real-world setting. Methods A retrospective analysis was performed using administrative databases linked to laboratory database, covering approximately 7 million health-assisted subjects. Adults prescribed with ROS/EZE as SPC or FC during January 2018-June 2020 were included and categorized in 2 cohorts. Index date (ID) was the first prescription of SPC or first simultaneous prescription of the 2 drugs (within 30 days interval). Patients were characterized during all available periods prior to ID and followed-up to end of data availability. Propensity score matching (PSM) was applied to minimize selection bias between cohorts; adherence was calculated as proportion of days covered (PDC): PDC<25% non-adherence; PDC=25-75% partial adherence; PDC>75% adherence, after PSM. Based on ESC/EAS 2019 guidelines, patients were stratified by CV risk profile. For a subgroup of patients (n=3,846) with plasma-LDL-C data availability (at ID and during first year of follow-up), the percentages of patients being above 55 mg/dl LDL-C for very-high risk, 70 mg/dl for high risk, and 116 mg/dl for other CV risk patients, and who reached these levels during follow-up were reported. Results The analysis included 25,886 patients in SPC cohort and 7,309 in FC. Post-PSM cohorts were balanced for their characteristics, including CV risk, and comprised 21,927 (SPC) and 7,309 (FC) patients. A higher percentage of patients were adherent to SPC vs FC (56.8% vs 44.5%, p<0.001). A lower percentage of non-adherent patients was found for the SPC vs FC (12.6% vs 27.4%, p<0.001). Among very-high, high and other CV risk patients, respectively, a 30%, 28% and 21% increase in the number of adherent patients was found for SPC vs FC [65.4% vs 50.4%, p<0.001 (very-high); 54.7% vs 42.7%, p<0.001 (high); 43.5% vs 35.9%, p<0.001 (other CV risk)] (Fig. 1). The proportion of very-high-CV risk patients reaching LDL-C ≤55mg/dl in the first year of follow-up was higher in SPC vs FC (35.4% vs 23.8%, p<0.001) (Fig.2). Similarly, among high-risk patients, 46.9% and 23.1% (p<0.001) of SPC and FC, respectively, reached ≤70 mg/dl LDL-C and among other CV-risk patients, 71.6% and 49.5% (p<0.001) of SPC and FC, respectively, reached ≤116 mg/dl LDL-C levels during first year of follow-up. Conclusions This real-world analysis in patients with hypercholesterolemia showed that treatment with ROS/EZE SPC vs FC could be associated with better medication adherence and lower LDL-C levels, whatever the CV risk category.