Outcomes research in pediatric liver transplant (LT) has focused on mortality and morbidity but there is a need to also evaluate functional outcomes. Standardized cognitive testing was administered to a cohort of children with infantile chronic liver disease who were transplanted at the University of Alberta during their preschool years. Thirty children had comprehensive assessments with the Bayley Scales of Infant Development or Wechsler testing. Patient variables potentially associated with cognitive delay were analyzed with multiple regression analysis. The mean DQ/IQ score (developmental quotient/intelligence quotient) was 81 +/- 17. Delay (DQ/IQ score < 70), and borderline delay (DQ/IQ 70-84) were each present in 27% of the cohort, with only 46% demonstrating normal cognition. Regression analysis demonstrated that the decreased IQ was associated with pretransplant growth retardation and elevated calcineurin inhibitor levels. Performance IQ had strong correlation with pretransplant growth retardation and elevated serum ammonia, R(2)= 45%, compared to verbal IQ that was associated was elevated calcineurin inhibitor levels, R(2)= 23%. Children post-LT are at high risk for cognitive delay or borderline delay. This is the first study to demonstrate the association calcineurin inhibitors with impaired IQ and also the unique finding of different variables predictive of impaired verbal intelligence quotient (VIQ) versus performance intelligence quotient (PIQ).