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Background: The ablative fractional laser can destroy the epidermal barrier and enhance the infiltration and distribution of drugs into the dermis. Objectives: This study was designed to investigate whether steroid delivery followed by the fractional ablative laser can prevent the formation of postthyroidectomy scar. Methods: This prospective split-scar design study recruited 12 adult female patients who underwent thyroidectomy between March 2018 and December 2018. The whole scar was treated with a fractional ablative carbon dioxide laser with topical 0.05% clobetasol propionate ointment only applied on the treatment side. The Patient and Observer Scar Assessment Scale (POSAS) questionnaire was used for outcome assessment at 1 year following the first treatment. The follow-up assessment by scar esthetic scale using digital photographs at 6 months and 1 year after first treatment was also done by three blinded plastic surgeons. Results: The POSAS revealed the improvement was not significant on vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion on the improvement (all P > 0.05). The digital photographs evaluation also did not reveal a significant difference between the treatment side and control side. The overall esthetic score in the assessment of digital photographs was 4.4 ± 1.5, 4.2 ± 1.9, and 3.4 ± 1.9 at 6 months, and 2.8 ± 1.9, 3.1 ± 1.9, and 2.4 ± 2.1 at 1 year, with 0–10 indicating totally identical to significantly different comparing the whole scar with surrounding normal skin. Conclusion: This prospective scar-split study revealed that the application of topical steroid after fractional ablative carbon dioxide laser has no significant effect to prevent the formation of postthyroidectomy scar.