OBJECTIVE: To assess treatment adherence to antipsychotic monotherapy in bipolar/manic disorder. METHODS: A total of 18,158 antipsychotic monotherapy treatment episodes for bipolar and manic disorders were identified from a claims database (1999-2003) representing 50 million US insured. Adherence measures included treatment compliance, captured by regularity of prescription refills, and treatment duration. Atypicals included risperidone, olanzapine, quetiapine, and ziprasidone; conventional agents included haloperidol, perphenazine, thioridazine, and thiothixene. Multiple regression adjusted for patient characteristics. RESULTS: Quetiapine alone had significantly (P<0.05) greater compliance than the conventional agents and had the highest compliance among the atypicals, which was significantly greater than for risperidone or olanzapine. Olanzapine and ziprasidone demonstrated significantly greater compliance than risperidone. Daily dose was negatively associated with compliance for all agents except quetiapine (P<0.05 for risperidone and the conventional agents), which had a positive, but non-significant association (P=0.074). Quetiapine and risperidone had significantly longer treatment duration than olanzapine, ziprasidone, and the conventional agents. All atypicals, except ziprasidone, had significantly lower odds of switching to another psychotropic compared with conventional agents; quetiapine had the lowest estimated odds ratio. CONCLUSION: According to claims data, treatment adherence for quetiapine appears higher than for other agents commonly prescribed for bipolar/manic disorder, possibly due to more favorable tolerability.