Abstract Background Radiation-induced fibrosis (RIF) is a chronic, progressive complication of radiotherapy in head and neck cancer with no effective treatment. It has significant impact on quality of life, including pain, poor cosmesis and head and neck contracture. Autologous fat grafting (AFG) is an emerging treatment for RIF. We systematically review the evidence for AFG as a treatment for Head and Neck RIF. Methods A systematic search strategy was designed a priori to established PRISMA guidelines. MEDLINE, Embase, Cochrane Library, and clinical trial registries were searched from inception. Eligibility criteria included any study investigating AFG as an intervention for RIF following head and neck cancer. Results Fourteen studies met the inclusion criteria, all of which reported physician-assessed aesthetic improvement. No study reported objective measurements of skin biomechanics. Functional outcomes were assessed in eight studies, using the UW-QOL V4, FOIS, VAS and penetration-aspiration scale. Psychological and quality of life outcomes were assessed in four studies via the UW-QOL V4, POS head/neck, SWOL-QOL, DAS24, SF-36 and VAS. Complication rates were low. Conclusions Clinical studies demonstrate that AFG may be an effective treatment for RIF in head and neck cancer patients. Outcome measures used varied between studies; development of a core outcomes set including PROMs and objective biomechanical measures of fibrosis would improve the quality of future research and a candidate list of outcomes is proposed.