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Systemic sclerosis (SSc) is a rare systemic autoimmune disease, characterized by progressive cutaneous and internal organ fibrosis. Orofacial manifestations of systemic sclerosis are extremely disabling and treatment options are limited. In this study, we aimed to assess the safety and efficacy of autologous fat grafting in the face of patients with systemic sclerosis. We enrolled 16 SSc patients suffering from facial sclerosis and limited mouth opening capacity. Autologous fat injection ranging from 15 to 40 ml was administered per patient, based on their face morphology. The patients were evaluated at baseline and 3 months after fat injection. Evaluations included mouth opening capacity, mouth handicap in systemic sclerosis (MHISS), Rodnan skin sclerosis score, skin biophysical properties using a sensitive biometrologic device with the assessment of cutaneous resonance running time (CRRT), volumizing and aesthetic effects based on pre- and posttreatment photographs, possible side effects, and global patient satisfaction. Clinical assessment showed autologous fat transfer significantly improved mouth opening capacity and the MHISS and Rodnan score of patients with facial scleroderma (p value