Schizophrenia is a highly disabling mental health disorder that imposes a considerable economic burden on a health care system. This paper aimed to examine the cost and effectiveness of alternative pharmaceutical interventions and the effects of family intervention (FI) for schizophrenia from the government perspective in order to introduce the most cost-effective intervention applicable to Vietnam. A Markov model was developed to estimate costs and health outcome over patients' lifetimes when using typical and atypical antipsychotic drugs, alone or in combination with family intervention. Health outcome was measured in terms of disability-adjusted life years averted. Monte Carlo simulation was used for uncertainty analysis. According to our findings, interventions using typical or atypical drugs combined with FI were found to be the most effective and least costly compared to a ‘do-nothing’ scenario. Interventions using atypical drugs alone were estimated to be much less favourable due to a considerably higher cost. This is a very first attempt on cost-effectiveness analysis of interventions for schizophrenia in Vietnam, and recommendations are made for future research to determine the most cost-effective intervention.