OBJECTIVES: Despite progress in the treatment of schizophrenia following the introduction of atypical antipsychotics in the late 1990s, current pharmacological options still carry limitations, as highlighted in a recent, pragmatic study in the US. Sertindole is an atypical antipsychotic with a good tolerability profile likely to favour long-term adherence, reductions in relapse and re-hospitalisation rates, and improvements in overall functioning. METHODS: A Markov model was developed to estimate the cost-effectiveness of sertindole compared with risperidone, olanzapine and aripiprazole in the management of schizophrenia in Hungary over a two-year period. Patients entered the model upon experiencing intolerance to their antipsychotic treatment during an episode of acute psychopathology. Confounding factors included drug-induced adverse events (extrapyramidal symptoms, weight gain, sedation, sexual dysfunction, diabetes), compliance, relapse and treatment setting. Effectiveness was defined as the length of time without relapse over the two-year evaluation period, and by Quality Adjusted Life Years (QALYs). Parameter estimates were based upon published literature and comparative clinical trial data. Resource use data were obtained from the Psychiatry Department, Semmelweis University (Budapest), and costs were evaluated from the Hungarian National Insurance perspective. RESULTS: The time without relapse (over 2 years) for patients receiving sertindole was equivalent to those with risperidone, olanzapine and aripiprazole (0.768, 0.768, 0.764 and 0.766, respectively). The average cost per patient for two years after starting treatment with sertindole equalled that of the other atypical antipsychotics. The costs per year without relapse were similar for sertindole treated patients compared with the atypical risperidone, olanzapine and aripiprazole treated patients (€ 15,435, 15,096, 15,925 and 15,712, respectively). Sensitivity analyses confirmed robustness of the model. CONCLUSIONS: With equivalent clinical benefits, a good tolerability profile and similar costs, sertindole is an additional valuable treatment alternative to other atypical antipsychotics available in Hungary.