Despite a well-recognized clinical benefit of the 2nd generation tyrosine kinase inhibitor nilotinib in patients with imatinib-resistant/-intolerant or newly diagnosed chronic myeloid leukemia, recent evidence suggests that nilotinib has a propensity to increase the risk of occlusive arterial events, especially in patients with pre-existing cardiovascular risk factors. Given the key role of lipids in cardiovascular diseases, we studied the plasma lipid profile and global cardiovascular risk prior to and during nilotinib therapy in a series of 27 patients in the setting of an observationalsingle-center study. Data from a minimum 1-year follow-up showed that nilotinib significantly increased total, low and highdensity lipoprotein cholesterol within 3 months. Consequently, the proportion of patients with non-optimal low density lipoprotein cholesterol increased from 48.1% to 88.9% by 12 months, leading to cholesterol-lowering drug intervention in 22.2% of patients. The proportion of patients with low levels of high density lipoprotein cholesterol decreased from 40.7% to 7.4% by 12 months. In contrast, a significant decrease in triglycerides was observed. Global cardiovascular risk worsened in 11.1% of patients due to diabetes or occlusive arterial events. Whether hypercholesterolemia was the main driver of occlusive arterial events was uncertain: a longer follow-up is necessary to ask whether nilotinib-induced hypercholesterolemia increaseslong-term risk of atherosclerotic diseases. Nevertheless, given keyatherogenicproperties of low density lipoprotein cholesterol, we conclude that when prescribing nilotinib, commitment to detect lipid disordersat baseline and during follow-up is mandatory given their frequency, requirement for lifestyle or drug intervention and potential for long-term cardiovascular complications.