OBJECTIVES: We assessed the effect of early intensive statin therapy on plaque inflammation in patients with acute coronary syndrome (ACS) by serial 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). BACKGROUND: Recurrent adverse ischemic events frequently occur within the first month after ACS despite adequate statin therapy. METHODS: We enrolled twenty statin-naïve patients with ACS and non-calcified carotid plaques on ultrasound. After obtaining FDG PET/CT of carotid arteries, all patients received atorvastatin, followed by a second FDG PET/CT of carotid arteries after one month of therapy. 13 patients completed initial and follow-up FDG PET/CT of carotid arteries. Maximum standardized uptake values (SUVmax) of given carotid plaques as well as plasma cholesterol levels were measured and compared. RESULTS: We quantified and tracked the statin-modulated alterations in inflammation of FDG-positive plaques in 13 patients. Statin therapy failed to reduce plaque inflammation at 1 month after ACS (mean SUVmax 2.2짹0.5 at baseline versus 2.0짹0.3 after therapy; p=0.174), while it significantly reduced plasma low-density lipoprotein cholesterol (LDL-C) (mean LDL-C 101.2짹21.1 mg/dL at baseline versus 70.7짹12.4 mg/dL after therapy; p<0.001). Notably, statin reduced carotid FDG uptake in nine patients but did not in four patients. Changes in SUVmax and plasma LDL-C levels were not correlated (r=-0.15, p=0.62). CONCLUSIONS: Serial FDG PET/CT demonstrates that statin alone fails to consistently reduce plaque inflammation within one month in patients with ACS.