In patients with localized scleroderma (LoS), facial deformity induced by subcutaneous atrophy greatly reduces life quality. Autologous fat grafting (AFG) is used for volume restoration but with low-fat retention due to various reasons. Adipose-derived stem cells (ADSCs) have shown potential effects in improving fat retention. We aimed to compare the feasibility and efficacy of improving fat retention in LoS patients among the ADSCs-assisted, the stromal vascular fraction (SVF)-assisted and conventional AFG methods. A pilot study with a 6-month follow-up among 18 LoS patients was conducted. Participants were randomly assigned into three AFG groups: conventional group, SVF-assisted group, and ADSCs-assisted group. The SVF-assisted group received SVF-assisted AFG at the SVF:fat ratio of 1:1. The ADSCs-assisted group received the mixture of ADSCs-enriched fat graft supplemented with 5 × 10 ADSCs/mL fat. Volume retention was measured by magnetic resonance imaging, and clinical photographs were taken for outcome evaluation. At sixth-month follow-up, the fat retention of ADSCs-assisted group was 49.83 ± 3.61%, significantly higher than 31.75 ± 1.73% of SVF-assisted group (P = .0004), and 21.86 ± 1.68% of the conventional group (P < .0001). A significant difference of the fat retention was also observed between the SVF-assisted and conventional group (P = .0346). No severe adverse events occurred during the procedure and follow-up. This pilot study suggests that ADSCs-assisted AFG is a safe, feasible, and attractive alternative to conventional and SVF-assisted AFG in the correction of facial atrophy of LoS patients. Future studies with large patient samples are needed for confirmation. (Chinese Clinical Trial Registry, ChiCTR1900025717).