OBJECTIVES: Attention-deficit hyperactivity/disruptive behavior disorders (ADHD/DBD) often lead to multiple placement transitions among youth in foster care. Increasingly, antipsychotic medications are used off-label to manage disruptive behaviors. There is limited evidence of the impact of antipsychotic management of ADHD/DBD on placement stability among fostered youth. This study is to investigate the association between antipsychotic initiation and time to first foster care placement transition among antipsychotic users and propensity-score matched nonusers.  METHODS: All youth (n=18,034) involved in foster care anytime from January 1, 2010 through March 31, 2014 in one Mid-Atlantic state were identified. Data were from child welfare administrative records linked with Medicaid claims. The index date was identified by filling the first antipsychotic prescription in 2010-2013. New antipsychotic users were restricted to youth with (1) continuous foster care involvement 180 days preceding and following the index date, (2) any diagnosis of ADHD, conduct disorder, oppositional defiant disorder, impulsive control, and (3) no antipsychotics 180 days before the index date. Propensity-score matched nonusers were defined as youth with no antipsychotic use in 2010-2013 and met the same selection criteria as the new antipsychotic users. The outcome was time to first foster care placement transition during a 180-day follow-up. Cox proportional hazard models estimated hazard ratios (HRs) associated with antipsychotic initiation, adjusting for demographic, clinical, and foster care characteristics.  RESULTS: Comparing new users to propensity-score matched nonusers, there was no difference regarding average days to placement transition (109 versus 113 days). The proportion experiencing a foster care placement transition (37% versus 36%) during the follow-up. The HR was 1.1 (95% CI: 0.7-1.6). CONCLUSIONS: Youth initiating antipsychotics had no significant reduction in foster placement transitions within the 180-day follow-up. Although antipsychotics are widely used for aggressive behaviors, a better understanding of clinical management of youth in foster care is needed to promote stable foster placement.