OBJECTIVES: To i) compare the relative costs of two leading atypical antipsychotics and ii) examine the contribution of cost drivers of inpatient schizophrenia care. METHODS: Data were pooled from a series of retrospective, single centre studies across 11 centers within 5 countries. Only patients with a diagnosis of schizophrenia or schizoaffective disorder were considered. RESULTS: A total of 601 patients received either risperidone (RIS; n=290) or olanzapine (OLA; n=311) as first line therapy after admission. There were no baseline differences between both groups. The two products showed equivalent efficacy rates (RIS: 78%, OLA: 77%; p=0.8) but RIS patients achieved efficacy sooner (median=10 days) than OLA patients (median=18 days; p=0.001). The mean modal daily doses were 4.9 mg (RIS) and 14.9 mg (OLA). OLA patients were more expensive (USD) than RIS patients in both daily treatment costs (RIS: mean=3.3; OLA: mean=6.5; p=0.0001) and daily all medication costs (RIS: mean=4.2; OLA: mean=7.3; p=0.0001). The contribution of cost drivers was examined through regression on the two key inpatient cost outcomes, daily all medications costs (log transformed) and length of stay (LOS; censored Cox regression). Daily all medication costs were independently affected by prior hospitalizations (+), choice of atypical (OLA higher than RIS) and dose of atypical (+) and these findings were over and above certain intermediate factors. Length of stay was affected by prior hospitalizations (-) and dose of atypical (+) again over and above certain intermediate factors. Despite being counterintuitive, the data clearly indicate that 1st episode patients stayed longest and the duration of stay continued to reduce with further admissions. CONCLUSION: The choice and dose of atypical is a major driver of inpatient therapy cost. In addition the prior disease span and severity, as measured by previous hospitalizations, is an important predictor of inpatient care costs.