Graft coronary artery disease is a significant cause of late graft failure and death after cardiac transplantation. HMG-coenzyme A reductase inhibitors have been used safely in children but their preventative effects against GCAD are not well known. We investigated whether atorvastatin when initiated early could prevent against the development of pediatric GCAD. Pediatric patients (transplanted between October 28, 1992 and July 9, 2004) were stratified into two groups based on whether or not they received atorvastatin early after transplant. Angiograms were reviewed by a single observer blinded to the treatment strategies and clinical outcomes. Actuarial survival method and the Mantel-Cox test were used to assess statistical significance. Freedom from GCAD was higher among those treated with atorvastatin early in the post-transplant course. One, three, and five-yr freedom from GCAD was significantly greater in the early treatment group (97%, 93%, and 93% respectively) compared with the control group (72%, 65%, and 60% respectively, p < 0.005). The early treatment group was also noted for fewer rejection episodes in the first post-transplant year. The use of atorvastatin when initiated early in the post-transplant course appears protective against graft coronary artery disease.