Objective: The study aimed to examine parent personality factors as predictors of parent medication knowledge and parent-report of child medication adherence. Method: Seventy-eight parents (Mage = 37.68, 87.2% female) of children (Mage = 8.89, range: 0–20 years) undergoing evaluation for a solid organ transplant were recruited. Parents completed questionnaires about their personality, knowledge of their child’s medications, and their child’s level of medication adherence. Results: Greater time since the child’s diagnosis predicted lower levels of medication knowledge, while higher levels of Neuroticism and Extraversion predicted greater levels of medication knowledge. Greater medication knowledge predicted greater levels of medication adherence, with this effect being moderated by conscientiousness. Children of parents with low knowledge and low conscientiousness had the lowest levels of adherence. Conclusions: Parent personality is significantly related to medication knowledge and children’s adherence prior to transplant. As parent personality is theoretically stable, Neuroticism (N), Extraversion (E), and Conscientiousness (C) serve as risk and protective factors that may influence medication knowledge and adherence even after transplantation. Parent medication knowledge and adherence are modifiable factors that would be appropriate targets for intervention during the pretransplant period.