OBJECTIVES: Pediatric Attention Deficit/Hyperactivity Disorder (ADHD) patients are usually prescribed combination of psychotropic agents. This study looked at the impact of atypical antipsychotic (AAP) use on long acting stimulant (LAS) persistence in children and adolescents with ADHD.   METHODS: This study used 4 years (January 2004 to December 2007) of IMS LifeLink™ claims data involving 6-16 years old youths with ADHD and at least 1 LAS prescription between July 2004 to December 2006 and continuous eligibility 6 months before and 1 years after the index LAS prescription. Persistence was measured by summing the total number of days a patient remained on the index LAS from the index prescription date with allowable gap of no more than 30 days. Multivariate Cox proportional hazards regression was used to examine the impact of concomitant atypical antipsychotic use on persistence of stimulants. RESULTS: The study cohort consisted of 39,981 subjects. Of these, 1,560 (3.90%) received LAS and AAP polypharmacy and the rest 38,421 (96.10%) received LAS monotherapy. Bivariate analyses revealed that concomitant users had longer persistence (by 71 days) than the stimulant alone users. Cox proportional hazards regression revealed that concomitant atypical antipsychotic use improved LAS persistence by 15% (HR=0.85, CI= 0.76-0.94) in comparison to the non-users among LAS recipients.  Other factors such as age, region, season, coexisting mental health conditions, use of co-medications, and general mental health status influenced the LAS treatment persistence among children and adolescents with ADHD. CONCLUSIONS: Use of atypical antipsychotics improved LAS treatment persistence in children and adolescents with ADHD. Various patient, clinical and treatment factors were associated with the LAS treatment persistence in ADHD youths. Understanding of these factors can help to improve persistence to LAS treatment.