Background <p>Atrophic acne scars (AAS) is one of the most common skin sequelae following acne vulgaris. Fractional laser has shown great therapeutic potential in recent years, but there is no recognized wound care standard after laser resurfacing. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown its value in many other acute wounds healing. Here, we investigated the efficacy and safety of topical recombinant human GM-CSF after 1927-nm fractional thulium fiber laser (TFL) in AAS treatment.</p> Methods <p>30 patients were enrolled and treated with TFL, then randomly assigned to rhGM-CSF-containing gel for 7 days or no intervention on each side. Photos, melanin index (MI), erythema index (EI), hydration, transepidermal water loss and improvement of lesions were assessed at 0, 3, 7, 14, 30 and 60 days.</p> Results <p>27 patients finally completed the study. Compared to TFL monotherapy, topical rhGM-CSF-containing gel significantly reduced duration of scabbing and skin erythema, and showed milder EI one week after TFL. MI on the rhGM-CSF side exhibited more pronounced decrease at the first and second months after TFL. Patients reported significant differences in sensations of burning, dryness and scabbing between two sides. Both sides yielded improvements in acne scars relative to baseline assessments, but no difference between them.</p> Conclusion <p>The combination of TFL and topical rhGM-CSF-containing gel showed significantly superior outcomes, manifesting as accelerated wound healing, improved postoperative patient comfort, and a reduced incidence of post-laser pigmentation.</p> Level of Evidence I <p>This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors <a href="http://www.springer.com/00266">www.springer.com/00266</a>.</p>