OBJECTIVES: Acute promyelocytic leukemia (APL) constitutes a distinct and rare variant of acute myeloid leukemia and is characterized by a high early mortality rate. Although current treatments (all-trans retinoic acid (ATRA), anthracyclines, including idarubicin, IDA, and conventional chemotherapy) are associated with high remission rates, cytotoxic effects of chemotherapy treatment are still a concern in the management of newly diagnosed APL. The objective of this study was to assess, from a Canadian perspective, the economic impact of arsenic trioxide (ATO) +ATRA compared to ATRA+IDA in the treatment of newly diagnosed APL. METHODS: The cost-effectiveness of ATO+ATRA compared to ATRA+IDA in the treatment of newly diagnosed APL was assessed over a lifetime horizon using a time-dependent Markov model. The model comprises four health states: complete remission, treatment failure or relapse, post-failure, and death. The length of each Markov cycle was one month for the first 48 months and one year thereafter. All patients started in the complete remission state and could move to other health states thereafter, according to the respective efficacy of each treatment. The model also takes into account the incidence of adverse events reported in a head-to-head trial. Utility or disutility values associated with each health state and adverse events were used to estimate the number of QALYs associated with each treatment. Analyses were conducted from both a Canadian Ministry of Health (MoH) and a societal perspective. RESULTS: Compared with ATRA+IDA, ATRA+ATO is associated with ICERs of $84,092/QALY and $80,946/QALY, from a MoH and societal perspective respectively. Results of the probabilistic sensitivity analysis indicated that the ICER remains below $100,000 in 99.82% and 99.98% of the simulations from a MoH and a societal perspective respectively. CONCLUSIONS: This economic evaluation suggests that ATO+ATRA can be considered a cost-effective option for the first-line treatment of newly diagnosed APL patients.