Carotid artery stenosis (CAS) is a leading cause of ischemic stroke. Plaque stabilization is a major management approach. Information about the ultrasonographical and clinical features associated with the progression of moderate internal carotid artery (ICA) stenosis (50-69%) could assist with prognostication and risk factor modifications. We evaluated 287 patients with moderate ICA stenosis (50-69%) and subsequently evaluated them at follow-up points at 12, 24, and 36 months. Patients were divided into three groups according to the degree of ICA stenosis: progression (70-99%, n = 48), stable (50-69%, n = 210), and regression (< 50%, n = 29). Responsible plaque thickness (RPT) across groups during follow-up was compared using a repeated measure ANOVA test. An ordinal regression was subsequently applied to identify risk factors for atherosclerosis progression. Male (P = 0.04), hypoechoic plaque (P < 0.01), smoking (P = 0.02), plaque ulceration (P = 0.05), and contralateral severe CAS or occlusions (P = 0.04) on ultrasound was more frequent in the progression group vs. other two groups. The ordinal regression revealed that only hypoechoic plaque (OR, 7.03; 95% CI, 3.34-14.81; P < 0.01) and contralateral ICA severe stenosis or occlusion (OR, 2.86; 95% CI, 1.41-5.80; P < 0.01) were independently associated with stenosis progression, while statin use was inversely associated with stenosis progression (OR, 0.26; 95% CI, 0.13-0.54; P < 0.01). Of note, symptomatic vs. asymptomatic moderate CAS at baseline was not associated with progression. For patients with moderate CAS, hypoechoic plaque, contralateral severe stenosis or occlusion on ultrasonography, and statin use are independently related to stenosis progression. Statin use may delay the progression of carotid stenosis.