Malignancies are frequently located in the head and neck region in children; their management usually requires radiotherapy, which has severe consequences on the growth of the craniofacial skeleton. The purpose of this work is to investigate the effects of radiation in the growing craniofacial skeleton in a rabbit model in vivo and in vitro and the possibilities of growth preservation using the cytoprotective drug Amifostine. The effects of radiation were studied in a single-dose radiation model, then in a more clinically-relevant fractionated-dose radiation model. Both radiation administration modes produced significant bone growth impairment. Administration of Amifostine prior to radiation significantly preserved craniofacial growth; this did not appeared to be related to vascularity as we did not demonstrated histomorphometric vessel changes or long-lasting changes in blood flow. Amifostine- treated animals had increased osteoblast counts, and improved bone turn-over compared to unprotected animals. In vitro, Amifostine enhanced the number of surviving cells after irradiation. This work suggests that radioprotection offers a viable pathway for the prevention of radiation-induced craniofacial bone growth inhibition and ensuing deformities.