Aim To explore the risk factors of atherosclerosis (As) in young and middle-aged premenopausal women by detecting the biochemical indicators and other exposure factors of young and middle-aged premenopausal women.Methods Young women (≤50 years old) who underwent physical examination in the Affiliated Hospital of Taishan Medical University from January 2013 to March 2016 were involved into this study. 390 young premenopausal women were enrolled, aged 26-50 years old, with an average of (45.6±4.4) years old. Carotid arteries of all the cases were assessed using PHILIPS iE 33 color Doppler echocardiography system with the liner probe of 7.5-10 MHz frequency. The arterial intima-media thickness and plaque were measured and recorded. According to the echo results, the cases were divided into 2 groups:As group (n＝191) and Control group (n＝199). Detailed inquiries were made on the past medical history and family genetic history of all the selected subjects, and blood pressure, height and body mass were measured. The indexes of blood lipid, fasting blood sugar, glycosylated hemoglobin, inorganic ions, liver function, kidney function, thyroid function, blood cell analysis and urine analysis were determined by automatic biochemical analyzer. Results The differences of age, grade 3 hypertension, diabetes history, long-term drinking history, smoking history (including passive smoking), family history of early onset coronary heart disease, low density lipoprotein cholesterol, total cholesterol, apolipoprotein B, β2 microglobulin, fasting blood sugar, glycosylated hemoglobin, urinary glucose, bicarbonate, chloride ion were statistically significant between the As group and the control group (P＜0.05). Univariate Logistic regression analysis showed that the incidence of As in young, middle-aged and premenopausal women was positively correlated with age, grade 3 hypertension, diabetes history, long-term drinking history, smoking history (including passive smoking), family history of early coronary heart disease, low density lipoprotein cholesterol, total cholesterol, apolipoprotein B, β2 microglobulin, fasting blood glucose, glycosylated hemoglobin, urinary glucose, blood bicarbonate, etc. Further multivariate Logistic regression analysis showed that age, grade 3 hypertension, long-term drinking history, smoking history (including passive smoking), family history of early onset coronary heart disease and elevated low density lipoprotein cholesterol were independent risk factors for As in young and middle-aged women. Conclusion Age, grade 3 hypertension, long-term drinking history, smoking history (including passive smoking), family history of early onset coronary heart disease and elevated low density lipoprotein cholesterol are independent risk factors for As in young and middle-aged premenopausal women.