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To evaluate predictors of persistence of attention deficit/hyperactivity disorder (ADHD) in a large sample of children with velo-cardio-facial syndrome (VCFS) with and without ADHD followed prospectively into adolescence.Children with VCFS with (n = 37) and without (n = 35) ADHD who were on average 11 years old at the baseline assessment and 15 years old at the follow-up assessment were comprehensively assessed with structured diagnostic interviews and assessments of behavioral, cognitive, social, school, and family functioning. Control participants both with and without ADHD were also followed prospectively.In adolescence, 65% of children with VCFS continued to have findings consistent with ADHD. Childhood predictors of persistence were higher rates of familial ADHD, having childhood depression, having higher levels of hyperactivity, and a larger number of intrusion errors on a verbal list learning test at baseline. Approximately 15% of children with VCFS who did not have ADHD at Time 1 met diagnostic criteria for ADHD at Time 2. All of these children had subthreshold ADHD symptoms at Time 1.These findings prospectively confirm that persistence of ADHD into adolescence in VCFS is predicted by childhood variables that have been previously documented in the non-VCFS ADHD literature.