OBJECTIVES: To compare the safety profile of nilotinib, observed in a large study of CML patients in a clinical practice setting to the product information of nilotinib and dasatinib. METHODS: Adult patients with imatinib resistant or intolerant Ph+ CML in chronic phase (CP), accelerated phase (AP), or blast crisis (BC) were recruited in this phase IIIb, open label, multi-center study. Patients received nilotinib 400 mg BID and were not permitted to dose escalate. Follow-up treatment in managing the hematological and non-hematological adverse event (AE), were recorded. Healthcare resource utilization was estimated by constructing six-month marginal cost increase in patients who received follow-up care for the management of AE. Cost data were obtained from MedStat MarketScan database that contained over 5000 CML patients. RESULTS: A total of 207 patients (172 CP pts, 15 AP pts, and 20 BC pts) were enrolled in the study between June 2006–October 2008. The percentage of patients with grade 3/4 hematological AEs suspected of being study drug-related in CP and AP were thrombocytopenia (12%, 20%), neutropenia (9%, 27%), and anemia (1.2%, 13%). The most frequent non-hematologic AEs (all grades) included rash, headache, nausea, and fatigue. The percentage of patients requiring additional therapy for the reported hematological AEs was less than 50% in most cases. Total medical costs associated with managing the AEs, estimated from MedStat cost data, for both hematological and non-hematological AEs were $6314 over a 6-month period. Medical costs associated with managing hematological AEs made up the majority of these costs. The estimated costs from this study were significantly lower compared to the estimated burden of the AEs in the product information for nilotinib or dasatinib ($9,730 and $12,372, respectively). CONCLUSIONS: Nilotinib related AE costs observed in this large clinical practice setting study compare favorably to the estimated costs from product information from nilotinib and dasatinib.