Objective <p>This study compared the efficacy and safety of botulinum toxin type A (BTX-A) injection and CO₂ ablative fractional laser combined with intense pulsed light (CO₂AFL-IPL) therapy in preventing hypertrophic scarring after thyroidectomy.</p> Approach <p>In this single-center, prospective, randomized controlled trial, 105 patients undergoing open thyroidectomy were assigned to three groups: silicone dressing (control), CO₂AFL-IPL therapy, or BTX-A injection. Scar outcomes were assessed over 12 months using the Patient and Observer Scar Assessment Scale (POSAS), modified Vancouver Scar Scale (mVSS), 3D imaging, colorimetry, and adverse event reports.</p> Results <p>Both BTX-A and CO₂AFL-IPL groups showed significantly improved POSAS and mVSS scores compared to the control group at 6 and 12 months (<i>p</i> &lt; 0.001), with no significant difference between the two treatment arms. BTX-A treatment had fewer adverse events and lower pain scores. Colorimetry and 3D imaging revealed no significant differences between groups.</p> Conclusion <p>Both BTX-A and CO₂AFL-IPL effectively prevented post-thyroidectomy scarring, each outperforming silicone dressings. While their efficacy was comparable, BTX-A offered greater convenience, safety, and patient comfort, making it a more practical option for routine clinical use, with CO₂AFL-IPL serving as an effective alternative where laser therapy is available.</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>