OBJECTIVES: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with approximately 1,000 to 1,500 new cases diagnosed each year in the United States (US). Trisenox (arsenic trioxide, ATO) is currently licensed for the treatment of patients with APL who are refractory to, or have relapsed from previous treatment with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. This analysis evaluated the cost-effectiveness of ATO+ATRA in the treatment of newly diagnosed low-to-intermediate risk APL in adult patients, compared to two other widely used regimens: ATRA+Ara-C+chemotherapy, and ATRA+Idarubicin (AIDA). Cost-effectiveness was measured as incremental cost per quality-adjusted life year (QALY) gained and per incremental cost per life year (LY) saved from a third-party payer perspective in the US.  METHODS: A Markov cohort model with monthly cycles and four health states (1^st-line stable disease, 2^nd-line stable disease, 2^nd-line disease event, and dead) was developed. Patients in the model begin treatment at age 45  and were followed until death. Eight months duration of ATO+ATRA was compared to either 15 months of ATRA+Ara-C+chemotherapy or 33 months of AIDA. Efficacy data (event-free survival.overall survival) were obtained from key clinical trials. Quality of life/health utility data were obtained from the literature. Costs were obtained from standard US data sources. Transition probabilities were estimated by calibrating the model to event-free and overall survival Kaplan-Meier curves for each treatment. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Compared to ATRA+Ara-C+chemotherapy, ATO+ATRA had incremental cost effectiveness ratios of $5,900/QALY gained and $4,800/LY saved. ATO+ATRA weakly dominated AIDA (had a lower incremental cost-effectiveness ratio and more QALYs and LYs) in newly diagnosed patients.  The results were robust to sensitivity analysis. CONCLUSIONS: The shorter and better-tolerated regimen of ATO+ATRA is a highly cost-effective strategy compared to ATRA+Ara-C+chemotherapy or AIDA in the treatment of newly diagnosed low-to-intermediate risk APL patients.