To evaluate and compare the treatment patterns, effectiveness, and safety of generic and branded atorvastatin in China.This multicenter, retrospective cohort study collected and analyzed data from patients who initiated atorvastatin therapy for the first time across 16 hospitals between 2020 and 2022. Treatment patterns included adherence, persistence, switching, augmentation. Absolute reductions of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, total cholesterol, and triglycerides, LDL-C reduction ≥ 50%, and adverse events were assessed to measure efficacy and safety. Propensity score matching was utilized to control for potential confounding variables.Data of 359,159 patients were reviewed. The results indicated a greater proportion of patients the generic atorvastatin group (5772/39742 [14.5%]) exhibited good adherence compared to those in the branded atorvastatin group (3157/39742 [7.9%]; P < 0.001) with an odds ratio of 1.97 (95% CI 1.88-2.06; P < 0.001). In the generic atorvastatin group, a smaller proportion of patients discontinued treatment (35,621/39,742 [89.6%]) compared to the branded group (36,390/39742 [91.6%]; P < 0.001) This difference in treatment persistence was further reflected in the calculated hazard ratio, which was 0.85 (95% CI 0.84-0.86; P < 0.001), indicating a reduced risk of discontinuation in the generic group. Efficacy outcomes were comparable between two groups (all P > 0.05). Both groups exhibited a comparable incidence of most adverse events. Less fasting plasma glucose increase and fewer new-onset diabetes were observed in the generic group (0.01 mmol/L [IQR 0-0.58] vs 0.16 mmol/L [IQR 0-0.73]; P = 0.009; 664/28640 [2.3%] vs 1244/28640 [4.3%]; P < 0.001).Generic atorvastatin had higher adherence and persistence and lower costs vs the branded drug, with no significant differences in efficacy and safety. Generic atorvastatin can be considered a viable option for dyslipidemia and atherosclerotic cardiovascular disease.© 2025. The Author(s).