OBJECTIVES: The objectives of this study were 1) to compare average total daily study drug cost of risperidone (n=120), olanzapine (n=153), and quetiapine (n=54) used as treatment for schizophrenia or schizoaffective disorder during an inpatient hospitalization, and 2) to compare medication utilization. METHODS: Retrospective data on inpatient drug utilization were collected on 327 patients at three acute inpatient mental health facilities through 60 days following initiation of study drug. All patients with an available psychiatric history had at least one previous psychiatric hospitalization. A propensity scoring method, modified for 3 treatment groups, was used to adjust for treatment selection bias. Factors which predicted treatment selection for all study drugs, for which adjustments were made, included age, gender, race, and facility. RESULTS: The average daily study drug cost was $4.35 less for risperidone than olanzapine (95% CI -$5.84, -$2.86), and $1.41 less for risperidone than quetiapine (95% CI -$3.89, $0.81). Between groups, there were no statistically significant differences in length of stay. Average daily dose for patients on study drug at time of discharge was 4.85mg (SD 2.29) for risperidone, 14.22mg (SD 5.44) for olanzapine, and 368.64mg (SD 230.52) for quetiapine. Total daily drug cost, including study drug and concomitant medications, for patients on study drug at time of discharge was $12.07 (SD 6.53) for risperidone, $16.33 (SD 6.56) for olanzapine, and $20.22 (SD 42.42) for quetiapine. CONCLUSIONS: Using a study design and analysis aimed at minimizing treatment selection bias, risperidone patients had a lower daily inpatient study drug cost than olanzapine (statistically significant) and quetiapine (not statistically significant) patients. In addition, differences in concomitant medication cost and utilization were present among treatment groups.