OBJECTIVES: Bipolar disorder (BPD) is highly prevalent and is associated with a significant economic burden. Antipsychotic drugs are one of the mainstream treatments for BPD. Asenapine is a new antipsychotic approved in Canada for the treatment to be used in monotherapy or co-therapy in BPD-I and schizophrenia. Asenapine has shown a comparable efficacy profile to olanzapine. However, in contrast to olanzapine, it is associated with a favourable metabolic profile and minimal weight gain. The objective of this study was to assess, from a Canadian perspective, the economic impact of asenapine compared to olanzapine in the treatment of BPD-I. METHODS: A combined decision tree and Markov model was constructed to assess the cost-utility of asenapine compared with olanzapine. The decision tree takes into account the occurrence of extrapyramidal symptoms (EPS), the probability of switching to a different antipsychotic, and the probability of gaining weight. The treatment used in case of switch was aripiprazole. The Markov model comprises the following states: long-term metabolic complications (diabetes, hypertension, CHDs, and stroke), fatal stroke, fatal CHD, and death by suicide or other causes. Due to limited data, asenapine was compared with olanzapine only. Analyses were conducted from both a Canadian Ministry of Health (MoH) and a societal perspective over a five-year time horizon with yearly cycles. RESULTS: In the treatment of BPD-I, asenapine is a dominant strategy over olanzapine from both a MoH and a societal perspective. Results of the probabilistic sensitivity analysis indicated that asenapine remains a dominant strategy in 99.2% of the simulations, and this result is robust to the many sensitivity analyses performed. CONCLUSIONS: This economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine in the treatment of BPD-I in Canada.