OBJECTIVES: Asenapine is a new antipsychotic approved in Canada for the treatment of schizophrenia (SCZ) and bipolar disorder I as monotherapy and co-therapy. Asenapine has shown a comparable efficacy profile to atypical antipsychotics. In contrast, however, to most atypical antipsychotics, it is associated with a favourable metabolic profile as well as with a minimal weight gain. The objective was to assess, from a Canadian perspective, the economic impact of asenapine compared to olanzapine, quetiapine, ziprazidone, aripiprazole. METHODS: A combined decision tree and Markov model was constructed to assess the cost-utility of asenapine compared with other atypical antipsychotics. 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 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. In the base-case analysis, asenapine was compared to olanzapine. Asenapine was also compared with atypical antipsychotics commonly used in Canada. 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 SCZ, asenapine is a dominant strategy over olanzapine from both an MoH and a societal perspective, and this result is robust to the many sensitivity analyses performed. Compared to quetiapine, asenapine is also a dominant strategy. Furthermore, asenapine has a favourable economic impact compared to ziprazidone and aripripazole, as these antipsychotics are not cost effective compared to asenapine, with an incremental cost-effectiveness ratio of $63,204/QALY and $1,485,625/QALY from a MoH perspective and $62,432/QALY and $1,485,623/QALY from a societal perspective, respectively.  CONCLUSIONS: This economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine and to most atypical antipsychotics used in Canada.