Abstract: Objective To explore the relationship between β2-microglobulin (β2M) and the stability of carotid atherosclerotic plaques. Methods Using the random number method, 239 individuals at risk for carotid atherosclerosis were screened from the outpatient and inpatient departments of neurology at Anhui Provincial Hospital. According to inclusion and exclusion criteria, 123 patients were finally included as research subjects. Based on the evaluation standards of carotid vascular lesions from the ultrasound, the subjects were divided into three groups: a normal carotid intima group (n=40), a stable plaque group (n=43), and an unstable plaque group (n=40). Their general clinical data, laboratory indices such as serum β2M, homocysteine (Hcy), cystatin C (CysC), and carotid ultrasound results were collected. Univariate analysis was conducted to compare differences in general clinical data and laboratory indices among the three groups. Multivariate logistic regression analysis was performed to determine whether β2M is an independent risk factor for carotid plaque instability. A receiver operating characteristic (ROC) curve was plotted to evaluate value of serum β2M levels for predicting carotid plaque instability.Results Univariate analysis showed that age, gender, hypertension, diabetes, β2M, Hcy, CysC, high-density lipoprotein cholesterol, and creatinine were statistical different among the normal carotid intima group, stable plaque group, and unstable plaque group (P<0.05). Binary logistic regression analysis indicated that serum β2M was an independent risk factor for carotid plaque instability; that is the higher the serum β2M level, the greater the likelihood of plaque instability. The ROC curve analysis showed that a serum β2M level of 1.875 mg/L could effectively predict plaque instability. Conclusions Serum β2M levels are an independent factor influencing plaque instability.