Second-generation antipsychotics have attracted practitioners' and policy-makers' attention, because of concerns over their health effects and costs. Comparative effectiveness data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-a high-profile National Institutes of Health (NIH)-funded study-have been used to argue for restricting coverage for these costly drugs. But concerns about the design of CATIE and its associated cost-effectiveness analysis and uncertainty about the precision of these findings raise questions about this interpretation. Our work suggests that additional research to increase the precision of comparisons of the effectiveness of antipsychotics would be well worth the cost.