OBJECTIVES: This study compared the cardiovascular safety of the addition of mood stabilizers or atypical antipsychotics to stimulant monotherapy in children and adolescents diagnosed with ADHD and bipolar disorder. METHODS: This retrospective cohort study used 2004-2007 IMS LifeLink™ Health Plan Claims Database. Children and adolescents aged 6 to 17 years diagnosed with ADHD and bipolar disorder who initiated a new treatment with stimulants were followed for 12 months to compare the safety of addition of mood stabilizers or atypical antipsychotics to stimulant monotherapy. Only patients who had continuous eligibility 6 months before and 12 months after the index stimulant date were selected. Exposure to a mood stabilizer or atypical antipsychotic agent after the initiation of the index stimulant treatment formed the primary exposure. The primary outcome was defined as the first hospitalization or emergency room (ER) visit for cardiovascular disorder identified using International Classification of Diseases- 9^th Revision, Clinical Modification (ICD-9 CM) codes. Cardiovascular risk was compared using time-varying Cox regression analysis adjusting for other cardiac risk factors. RESULTS: Of the 1,769 ADHD and bipolar patients, 48.28% were prescribed stimulants only, 16.68% were on mood stabilizer-stimulant combination and 35.05% were on antipsychotic-stimulant combination therapy. The incidence of cardiovascular events were 5.15% in the stimulants-only group, 4.75% in the mood stabilizer-stimulant group and 8.87% in antipsychotic-stimulant group. No statistically significant difference was found in the risk of cardiovascular events among patients with mood stabilizer-stimulant combination (HR=0.98, 95% Confidence Interval, 95% CI: 0.49-1.99) or antipsychotic-stimulant combination (HR=0.57, 95% CI: 0.31-1.05) compared to stimulant monotherapy. CONCLUSIONS: The current study did not find any difference in the cardiovascular risk after addition of mood stabilizer or atypical antipsychotic to stimulant monotherapy in patients with ADHD and bipolar disorder. More studies are needed to evaluate overall safety profiles of these therapeutic combinations in patients with comorbid ADHD and bipolar disorder.