There has been limited consideration and empirical studies on treatment-resistant bipolar disorder (TRBD). This exploratory study was designed to identify factors contributing to TRBD in patients with a bipolar (I or II) disorder. Patients were categorized with “low,” “medium,” or “high” levels of treatment resistance based on a) the total number of psychiatric medications received and, for a second analysis, b) the number of mood stabilizer medications received. The study identified a number of factors associated with TRBD, such as being female and older and having an older age at illness onset, a higher incidences of family depression, less likelihood of being in paid employment, a higher number of lifetime stressors, medical conditions and comorbid anxiety disorders, a different personality and temperament profile, and more regular use of benzodiazepines. There were few factors associated with TRBD when defined by number of mood stabilizers trialed. Potential explanations for these findings were explored.