OBJECTIVES: To compare health care resource utilization and costs associated with dasatinib versus nilotinib treatment as second-line therapies in CML patients. METHODS: Two claims databases were combined (MarketScan and Ingenix Impact, January 2002 - December 2008) to identify patients diagnosed with CML (ICD-9 code 205.1x) and received ≥1 prescription of dasatinib or nilotinib. Patients were required to have continuous enrollment ≥1 month prior to and after the index date. The index date was defined as the first prescription for dasatinib or nilotinib. Patients were followed for up-to 6 months from the index date to the earliest of the termination of health care plan enrollment, or end of data availability. Negative binomial regression models were used to compare health care resource utilization between the two groups.  Results were reported as unadjusted and adjusted incidence rate ratios (IRR). Healthcare costs were compared and reported as unadjusted and adjusted cost differences. These were estimated for each cost component using generalized linear models or two-part models. Multivariate regressions controlled for age, gender, and CML disease complexity. RESULTS: A total of 230 CML patients receiving a second-line TKI (186 dasatinib and 44 nilotinib) were studied. During the study period, dasatinib patients had significantly more medical visits (IRR=1.32, p=.028). Dasatinib patients had 36% more hospital days but the difference was not statistically significant (IRR=1.36, p=0.664). Over the 6–month follow-up period, patients on dasatinib incurred $18,328 (p<.001) more in total medical services and $6,367 (p=0.04) less in pharmacy costs, resulting in a higher net total healthcare cost of $12,039 (p=.035). The difference in medical costs was mainly explained by the difference of inpatient costs ($12,480; p=<.001) and outpatient costs ($5,035; p=.001). CONCLUSIONS: Among CML patients treated with a second-line TKIs, dasatinib patients incurred higher total healthcare costs and more frequent healthcare resource utilization than nilotinib patients.