Initial research supports the use of propranolol to prevent posttraumatic stress disorder (PTSD); research has not examined pharmacological prevention for children. Twenty-nine injury patients (ages 10-18 years old) at risk for PTSD were randomized to a double-blind 10-day trial of propranolol or placebo initiated within 12 hours postadmission. Six-week PTSD symptoms and heart rate were assessed. Although intent-to-treat analyses revealed no group differences, findings supported a significant interaction between gender and treatment in medication-adherent participants, Delta R(2) = .21. Whereas girls receiving propranolol reported more PTSD symptoms relative to girls receiving placebo, Delta R(2) = .44, boys receiving propranolol showed a nonsignificant trend toward fewer PTSD symptoms than boys receiving placebo, Delta R(2) = .32. Findings inform gender differences regarding pharmacological PTSD prevention in youth.