Background: There are claims that the extra costs of atypical (second-generation) antipsychotic drugs over conventional (first-generation) drugs are offset by improved health-related quality of life. Aims: To determine the relative costs and value of treatment with conventional or atypical antipsychotics in people with schizophrenia. Method: Cost-effectiveness acceptability analysis integrated clinical and economic randomised controlled trial data of conventional and atypical antipsychotics in routine practice. Results: Conventional antipsychotics had lower costs and higher quality-adjusted life-years (QALYs) than atypical antipsychotics and were more than 50% likely to be cost-effective. Conclusions: The primary and sensitivity analyses indicated that conventional antipsychotics may be cost-saving and associated with a gain in QALYs compared with atypical antipsychotics.