Background <p>Fractional laser therapy is a cornerstone for atrophic acne scar treatment. While both ablative fractional CO₂ and non-ablative fractional Er:Glass&#xa0;lasers are widely used, comprehensive comparative data on their efficacy, patient satisfaction, and complication profiles remain limited. This meta-analysis aimed to quantitatively compare these outcomes.</p> Methods <p>A systematic literature search was performed in PubMed, Web of Science, and Cochrane Library up to March 5, 2025. Prospective randomized trials directly comparing Er:Glass&#xa0;and CO₂ lasers for atrophic acne scars were included. Outcomes were effective rate (&gt;50% improvement), patient satisfaction rate, pain (VAS), post-inflammatory hyperpigmentation (PIH) rate, duration of crusting and duration of erythema. Data were pooled using meta-analysis in R (meta package).</p> Results <p>Four studies (98 participants) were included. Pooled analysis showed no significant difference in effective rate (OR = 0.43, 95% CI 0.03–5.98) or patient satisfaction rate (OR = 0.70, 95% CI 0.08–6.25) between lasers. PIH rates were similar (OR = 0.50, 95% CI 0.17–1.45). Er:Glass&#xa0;was associated with significantly less pain (MD = −1.70, 95% CI −2.13 to −1.28), shorter duration of crusting (MD = −3.53, 95% CI −4.55 to −2.52), and duration of erythema (MD = −3.16, 95% CI −3.58 to −2.74).</p> Conclusion <p>Er:Glass and CO₂ fractional lasers demonstrate comparable efficacy and patient satisfaction for atrophic acne scars. Er:Glass offers significant advantages in reduced procedural pain and shorter recovery time, supporting its use as a safer alternative with similar effectiveness.</p> Level of Evidence III <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>