OBJECTIVES: Acute promyelocytic leukemia (APL) constitutes a rare disease characterized by a high mortality rate at early stage of treatment. Current first-line treatments consist of all-trans retinoic acid (ATRA), anthracyclines and conventional chemotherapy (CT). Although APL has currently a good prognosis, 20 to 30% of patients who achieved remission still relapse and are further resistant to the treatment previously administrated. The objective of this study was to assess, from a Canadian perspective, the economic impact of arsenic trioxide (ATO) compared to ATRA+CT in the treatment of relapsed/refractory APL. METHODS: The cost-effectiveness of ATO compared to ATRA+CT in the treatment of relapsed/refractory APL was assessed over a lifetime horizon using a time-dependent Markov model. The model comprises five health states: induction, second remission, treatment failure or relapse, post-failure, and death. The length of each Markov cycle was one month for the first 24 months and one year thereafter. All patients started in the induction 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 grade 3-4 adverse events reported in clinical trials. 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+CT, ATO was associated with incremental cost-effectiveness ratios of $18,380/QALY from a MoH perspective and $20,156/QALY from a societal perspective. Results of the probabilistic sensitivity analysis indicated that ATO remains a cost-effective strategy in 99.96% and 92.45% of the simulations, from a MoH and a societal perspective respectively. CONCLUSIONS: This economic evaluation suggests that ATO is a cost-effective strategy compared to ATRA+CT in the treatment of relapsed/refractory APL in Canada.