OBJECTIVES: To examine the prevalence and time to psychotropic polypharmacy in children with Attention-Deficit Hyperactivity Disorder (ADHD). METHODS: This retrospective longitudinal database analysis of medical, pharmacy and eligibility data was performed on Medicaid enrollees from four states – Texas, New York, California, and Illinois – during a 3-year period (January 2003 and December 2005). ADHD patients were identified on the basis of one or more ADHD diagnosis and stimulant (short-acting [SAS], intermediate-acting [IAS] or long-acting [LAS]) prescription(s). New stimulant users were selected if the index stimulant prescription was filed between July 1, 2003 and June 30, 2005 with no previous stimulant drug prescription in the preceding 6 months. Additional eligibility criteria included continuous Medicaid eligibility 180 days pre- and post- index date and no multiple index stimulant type claims. Psychotropic polypharmacy episode was defined as ≥30 consecutive days of non-stimulant therapy overlapping with the index stimulant therapy. The time to psychotropic polypharmacy was assessed by calculating the time from the index stimulant date to the first day of polypharmacy treatment episode using the Cox proportional Hazards model. RESULTS: Among the 63,362 ADHD patients, 19.95% of SAS users, 24.26% of IAS users and 29.56% of LAS users received combination pharmacotherapy involving their index stimulant. Median survival time to psychotropic polypharmacy was found to be 299, 232, and 330 days in the SAS, IAS and LAS treatment groups respectively. Recent inpatient psychiatric visit(s) and younger age emerged as the common risk factors predicting index stimulant and a psychotropic co-prescription. In addition, race/ethnicity and a comorbidity of tics were also identified as predictors for LAS-related psychotropic polypharmacy. CONCLUSIONS: Over one in five new stimulant users with ADHD received a concomitant non-index stimulant prescription within a year of commencing stimulant therapy. Demographic and clinical characteristics seem to play a key role in psychotropic polypharmacy in children with ADHD.