OBJECTIVES: Bipolar disorder has an associated economic burden due to its treatment, including medication and hospitalization costs as well as costs associated with treatment of comorbid medical conditions. This study compared healthcare costs in patients treated with a mood stabilizer and adjunctive aripiprazole versus adjunctive olanzapine, quetiapine, risperidone or ziprasidone. METHODS: A retrospective propensity score-matched cohort study was conducted in the LabRx integrated claims database from January 2003 through December 2006. Patients aged 18–65 years with bipolar disorder and 180 days of pre-index enrolment without atypical antipsychotic therapy and 90 days post-index enrolment were eligible for inclusion. Mood stabilizer therapy was initiated prior to index atypical prescription. Generalized gamma regressions were used to compare the total healthcare costs of patients treated with adjunctive aripiprazole and patients treated with adjunctive olanzapine, quetiapine, risperidone or ziprasidone. RESULTS: After controlling for differences in baseline characteristics and pre-index cost, psychiatric costs and subtotal psychiatric and general medical cost were significantly higher for all adjunctive atypical antipsychotics than adjunctive aripiprazole (p<0.001). There was no significant difference in general medical costs between aripiprazole and ziprasidone, olanzapine, or quetiapine. Aripiprazole medication costs were significantly higher than for quetiapine and risperidone (p<0.001) but not olanzapine or ziprasidone. Total healthcare costs were significantly higher for ziprasidone, olanzapine, or risperidone (p<0.001) than aripiprazole but not for quetiapine. CONCLUSIONS: Adjunctive aripiprazole may have economic benefits over other atypical antipsychotics in terms of lower psychiatric treatment costs of care than adjunctive olanzapine, quetiapine, risperidone or ziprasidone, and lower total healthcare costs than adjunctive olanzapine, risperidone or ziprasidone.