Objectives: Schizophrenia is the third leading cause of loss of life years in Thailand. Currently, aripiprazole is the latest drug for the treatment of acute schizophrenia in Thailand, but its cost-effectiveness has not been studied. The purpose of this study was to investigate the cost-effectiveness of aripiprazole compared with risperidone. Methods: A Markov model was used to evaluate total costs and quality-adjusted life years (QALYs) over a lifetime horizon from a societal perspective. Clinical effectiveness was retrieved from previous studies. All cost data and mortality rates were retrieved from Thai data. Results: The results revealed that the total cost of the treatment with aripiprazole was 691,469.06 Baht compared to 692,200.88 Baht for risperidone, and the QALYs were 15.75 and 15.45 years, respectively. The acceptability curves demonstrated that the probability of aripiprazole being cost-effective was 97.5% of the willingness-to-pay, being 1.2 times the Thai gross national income per capita. Conclusions: Treatment of acute schizophrenia in Thailand with aripiprazole was showed greater QALYs and lower cost than treatment with risperidone. Treatment with aripiprazole is a dominant alternative. The results of this study could contribute to appropriate decision-making by policymaker.