OBJECTIVES: To evaluate the cost-effectiveness of several sequential treatment strategies for chronic myeloid leukemia (CML) dependent on early molecular response (EMR) in the Austrian healthcare context. METHODS: We adapted a previously developed Markov state-transition model to incorporate different treatment options (imatinib, dasatinib, nilotinib) dependent on achievement of EMR after 3 months. We analyzed eight sequential treatment strategies using cohort simulation over a lifelong time horizon. Model parameters were extracted from published literature, epidemiological and economic databases. We applied a 3% discount for health outcomes and costs. We analyzed 3 different base-case scenarios for patients not achieving an EMR after 3-months of imatinib treatment that were switched to a second-generation TKI, assuming three different effectiveness for these second-generation TKIs. Comprehensive sensitivity analyses were conducted. RESULTS: The base-case analysis resulted in two non-dominated strategies: (1) imatinib, followed by nilotinib in case of non-achieved EMR at 3 months and dasatinib after treatment failure or imatinib continuation in case of achieved 3-month EMR and nilotinib after treatment failure; (2) nilotinib followed by its continuation in case of non-achieved EMR at 3 months or switch to imatinib in case of achieved 3 month EMR and dasatinib after treatment failure. Depending on the scenario, strategy 2 resulted in an incremental cost-effectiveness ratio (ICER) of €84,200/QALY, €118,500/QALY or €142,200/QALY gained compared to the baseline strategy. Remaining strategies were excluded due to dominance. Sensitivity analyses on generic pricing of imatinib showed that starting with a more potent second-generation TKI and switching to imatinib after an achieved EMR are the preferred strategies. CONCLUSIONS: Based on our analyses, we suggest nilotinib and its continuation for non-achieved EMR at 3 months or switch to imatinib after achieved 3-month EMR and dasatinib after treatment failure as a cost-effective strategy for Austria if the willingness-to pay threshold is at least around €120,000/QALY.