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Introduction: Dark under-eye circles or periorbital hyperpigmentation constitute a prevalent and challenging cosmetic problem with diverse etiologies and types. While modifying exacerbating habits can provide partial relief for the pigmentary and vascular factors associated with this condition, and despite the abundance of available treatment options, there is currently a lack of gold-standard evidence-based treatments proposed for curing this disorder., Objectives: This study aimed to assess the safety and effectiveness of carboxytherapy in treating periorbital hyperpigmentation., Material and Methods: In this 4-week single-arm clinical trial, 20 eligible Iranian patients with symmetric periorbital hyperpigmentation received weekly intradermal carboxytherapy. The treatment involved administering 10-20 mL of CO2 at a rate of 20 mL/min and a temperature of 15°C for a duration ranging from a few seconds to 1 min. Follow-up assessments were conducted 1 month after the final session. The primary outcome was defined as the changes in ΔE or the variations in pigmentation observed between the orbital and extra-orbital skin before and after the trial., Results: The patients reported satisfaction with the statistically significant reduction in hyperpigmentation achieved through carboxytherapy in the lateral (p = 0.002), middle (p = 0.001), and medial (p = 0.001) regions of the periorbital area. The total response rate of the patients was estimated at 20%. Patient satisfaction exceeded ΔE changes, with no significant linear relationship (p = 0.084)., Conclusion: Carboxytherapy can be proposed as an effective and safe treatment for periorbital hyperpigmentation., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)