There are currently three tyrosine kinase inhibitors (TKI) approved for first-line treatment of chronic myeloid leukemia (CML). Historically, imatinib, a first-generation TKI (1GTKI), was the standard of care for patients with CML. Both nilotinib and dasatinab, second-generation TKIs (2GTKI), received FDA approval as first-line options for CML in 2010. This study examined the association between patients newly initiating a 1GTKI compared to a 2GTKI and treatment patterns, adherence, health services utilization and healthcare costs. A retrospective cohort study of commercial and Medicare patients newly initiating TKI therapy between June 1, 2010 and December 31, 2011 were identified. Patients who were new users, continuously enrolled for 4 months during the baseline period, between the ages of 18 and 89 years old at the index date, and had a diagnosis for CML were included. Risk adjustment methods were used to evaluate time to treatment interruption and regimen change. Multivariate logistic regression was used to investigate the association between TKI therapy and adherence. Generalized linear models were used to examine the association between TKI therapy and (1) health services utilization and (2) healthcare costs during the 12 months follow-up period. Of the 368 patients newly initiated on TKI therapy, 237 (64%) initiated therapy on 1GTKI. Initiating a 2GTKI was associated with a higher risk of treatment interruption (HR: 1.59, 95% CI 1.18-2.12, unadjusted model; HR: 1.48, 95% CI 1.08-2.02, multivariable model; HR 1.50, 95% CI 1.10-2.04, propensity score quintiles model). Although the majority of patients with a treatment interruption re-initiated the index medication or changed medications, 15% of patients who initiated a 1GTKI and 30% of patients who initiated a 2GTKI discontinued treatment for the remainder of the study period. There was no association between initiating a 2GTKI versus 1GTKI and regimen change or adherence. Although mean adherence was higher for the 1GTKI cohort compared to the 2GTKI cohort, mean adherence was low in both cohorts (PDC=0.79 and PDC=0.68, respectively, p=0.007). Patients who initiated 2GTKI incurred more inpatient hospitalizations and ER visits compared to 1GTKI. Regression models demonstrated that initiating therapy with a 2GTKI was associated with higher total and TKI-related costs.