Nilotinib is currently approved for the treatment of chronic myeloid leukemia (CML) in chronic (CP) and accelerated phase (AP) after failure of imatinib and in newly diagnosed patients. Atherosclerotic events were retrospectively reported in patients with baseline cardiovascular risk factors during nilotinib treatment. We estimated the risk of developing atherosclerotic events in patients treated with second or first-line nilotinib, with a median follow-up of 48 months, by retrospectively applying the SCORE chart proposed by the European Society of Cardiology (ESC) and evaluating risk factors at baseline (diabetes, obesity, smoking, and hypertension). Overall, we enrolled in the study 82 CP patients treated frontline (42 CP patients at the dose of 600 mg BID) or after failure of other tyrosine kinase inhibitors (40 CP patients treated with 400 mg BID). The SCORE chart is based on the stratification of sex (male vs female), age (from 40 to 65 years), smoker vs non-smoker, systolic pressure (from 120 to 180 mm Hg), and cholesterol (measured in mmol/l, from 150 to 300 mg/dl). For statistical purposes, we considered patients subdivided in low, moderate, high (with a score >5), and very high risk. There were 48 males and 34 females, median age 51 years (range 22-84). According to WHO classification, 42 patients were classified as normal weight (BMI <25), 26 patients were overweight (BMI 26 ≤ 30), and 14 were obese (BMI >30). Retrospective classification according to the SCORE chart revealed that 27 patients (33 %) were in the low-risk category, 30 patients (36 %) in the moderate risk category, and 24 patients (29 %) in the high risk. As regards risk factors, we revealed that 17 patients (20.7 %) had a concomitant type II controlled diabetes (without organ damage), 23 patients (28 %) were smokers, 29 patients (35 %) were receiving concomitant drugs for hypertension, and 15 patients (18 %) had concomitant dyslipidemia. Overall, the cumulative incidence of atherosclerotic events at 48 months was 8.5 % (95 % CI, 4.55-14.07): None of the low-risk patients according to the SCORE chart experienced atherosclerotic events compared to 10 % in the moderate risk category and 29 % in the high risk (p = 0.002). Atherosclerotic-free survival was 100, 89, and 69 % in the low, moderate, and high-risk population, respectively (p = 0.001). SCORE chart evaluation at disease baseline could be a valid tool to identify patients at high risk of atherosclerotic events during nilotinib treatment.