The study goals were: a) to determine factors associated with diagnostic change from bipolar disorder (BPD) to other disorders and vice versa and b) to focus on subjects with diagnostic changes specifically between BPD and schizophrenia. A total of 936 subjects with at least four hospitalizations within 7 years were identified from the hospital database to study the first goal. A subset of 443 subjects with initial and final diagnoses of bipolar disorder and/or schizophrenia was used for the second goal. Sixty-eight(28.9%) of 235 subjects with an initial diagnosis of BPD changed to another diagnosis, whereas 113 (16.1%) of 701 subjects with a non-BPD diagnosis had a diagnostic change to BPD at a later episode. Only 8 of 43 subjects entering the study period with a diagnosis of schizoaffective disorder still had that diagnosis at the end of the period. Results suggest that diagnostic flux between BPD and other disorders, especially schizophrenia, is relatively frequent. Gender, ethnicity, and substance abuse/dependence have prominent roles in these diagnostic changes. Severity and variability of the course of illness and progression of concurrent substance use disorder are crucial to understanding diagnostic flow in BPD.