Background: The purpose of this study was to compare the efficacy and safety of high-dose atorvastatin (40 mg) versus high-dose rosuvastatin (20 mg) in Egyptian patients with type 2 diabetes and previous acute coronary syndrome history. Materials and methods: This open-labeled prospective, randomized clinical trial compared once daily atorvastatin 40 mg (Ator ® ) versus once daily rosuvastatin 20 mg (Crestor ® ). The primary outcome was the 50% reduction in low-density lipoprotein cholesterol levels at 12 weeks. The secondary outcome was the achievement of low-density lipoprotein cholesterol level < 55 mg/dL. Results: A total number of 108 patients had a significant percentage of improvement in atorvastatin arm (n = 59) and rosuvastatin arm (n = 49) in low-density lipoprotein cholesterol, total cholesterol, triglycerides, and high-density lipoprotein-cholesterol achieved (p ≤ 0.05). In atorvastatin arm, 32.2% of patients achieved fifty percent reduction in low-density lipoprotein cholesterol while 34.7% of patients in rosuvastatin arm (p > 0.05). Twenty percent of patients achieved low-density lipoprotein cholesterol < 55 mg/dL in atorvastatin group compared to eighteen percent only in rosuvastatin group (p > 0.05). Regarding safety, the mean difference in liver transaminases was non-significant between the two groups (p > 0.05). Muscular symptoms were experienced by 1.7% patients receiving atorvastatin 40 mg and 10.2% of those receiving rosuvastatin 20 mg (p > 0.05). Conclusions: In Egyptian context, both high doses statin therapy were comparable regarding efficacy and safety in patients with type 2 diabetes and previous history of acute coronary syndrome. The Clinicaltrial.gov registration ID is: NCT05306990.