To identify factors associated with incident cardiovascular events and metabolic disturbance in children and adolescents treated with antipsychotics. A retrospective cohort design evaluating Medicaid medical and pharmacy claims. South Carolina's Medicaid program covering outpatient and inpatient medical services and medication prescriptions from January 1, 1996, through December 31, 2005. A treatment cohort of 4140 children and adolescents prescribed 1 of 5 atypical or 2 conventional antipsychotics, and a random sample of 4500 children not treated with psychotropic medications. Main Exposure Antipsychotics. Incidence/prevalence rates for obesity, type 2 diabetes mellitus, dyslipidemia, cardiovascular events, cerebrovascular events, hypertension, and orthostatic hypotension. Compared with the control sample, the treated cohort had a higher prevalence of obesity (odds ratio [OR], 2.13), type 2 diabetes mellitus (OR, 3.23), cardiovascular conditions (OR, 2.70), and orthostatic hypotension (OR, 1.64). In the treated cohort, patients exposed to multiple antipsychotics were at significantly higher risk for incident obesity/weight gain (OR, 2.28), type 2 diabetes mellitus (OR, 2.36), and dyslipidemia (OR, 5.26). Incident cardiovascular events were more likely with the use of conventional (OR, 4.34) or multiple (OR, 1.57) antipsychotics and mood stabilizers (OR, 1.31). Incident orthostatic hypotension was more prevalent in those coprescribed selective serotonin reuptake inhibitors (OR, 1.77) and mood stabilizers (OR, 1.35). Antipsychotics are associated with several metabolic and cardiovascular-related adverse events in pediatric populations, especially when multiple antipsychotics or classes of psychotropic medications are coprescribed, controlling for individual risk factors.