Background: The objective of the study is to estimate the protective role of statins in patients with acute coronary syndrome (ACS) through modulation of annexin A1 (AnxA1) serum levels. Methods: A total number of 63 patients with ACS were recruited compared with 25 healthy control subjects. The enrolments were divided into – Group (A): Patients with ACS on atorvastatin ( n = 20), Group (B): Patients with ACS on rosuvastatin ( n = 20), Group (C): Patients with ACS but not on statin therapy ( n = 23), and Group (D): Healthy controls ( n = 25). Body mass index and both systolic blood pressure and diastolic blood pressures were measured. Lipid profile, atherogenic index, cardiac risk ratio, cardiovascular risk index, and human AnxA1 level were estimated. Results: AnxA1 serum level was higher in patients with ACS (3.35 ± 0.84) compared with healthy controls (1.71 ± 0.91) and nonstatin using patients (1.47 ± 0.76) ( P = 0.005). Conclusion: AnxA1 serum level is reduced in patients with ACS compared with healthy controls. Patients with ACS on statins therapy showed a higher level of AnxA1 compared with patients with ACS but not on statin therapy.