Abstract Aim: To compare the effectiveness and safety of two high-intensity atorvastatin doses (40mg vs. 80mg) among acute coronary syndrome (ACS) patients. Methods: This retrospective observational cohort study using real-world data included patients admitted with ACS to the Heart Hospital in Qatar between January 1, 2017 and December 31, 2018. The primary endpoint was a composite of cardiovascular disease (CVD)-associated death, non-fatal ACS, and non-fatal stroke. Cox proportional hazard regression analysis was used to determine the association between the two high-intensity atorvastatin dosing regimens and the primary outcome at 1 month and 12 months post-discharge. Results: Of the 626 patients included in the analyses, 475 (75.9%) received atorvastatin 40mg, while 151 (24.1%) received atorvastatin 80mg following ACS. Most of the patients were Asian (73%), male (97%) with a mean age of 50 years, and presented with ST-elevation myocardial infarction (60%). The incidence of the primary effectiveness outcome did not differ between the atorvastatin 40mg and 80mg groups at 1 month (0.8% vs. 1.3%; aHR= 0.59, 95% CI 0.04-8.13, p= 0.690) and at 12 months (3.2% vs. 4%; aHR= 0.57, 95% CI 0.18-1.80, p= 0.340). Similarly, the use of the two doses of atorvastatin resulted in comparable safety outcomes, including liver toxicity, myopathy, and rhabdomyolysis with an event rate of < 1% in both groups. Conclusion: The use of atorvastatin 40mg in comparison to atorvastatin 80mg in patients with ACS resulted in similar cardiovascular effectiveness and safety outcomes.