Objective To investigate the therapeutic efficacy and safety of carbon dioxide (CO2) fractional laser in treating periorbital syringoma.Methods Twenty-eight patients with syringoma were treated with ultrapulse CO2 fractional laser.Digital photos were taken before the treatment,1 month and 3 months after the treatment to evaluate the efficacy.The recovery process and side effects were also recorded to assess the safety.Dermatologists rated the efficacy in 0-4 points scales.The patients assessed overall satisfaction in 0-4 point scales.Results One month after the treatment,74.99 % of the patients had improvement rate of over 50 % and 67.85 % of the patients were satisfied or very satisfied with the overall efficacy.Three months after treatment,78.57 % of the patients had improvement rate of over 50 % and 71.42 % of the patients were satisfied or very satisfied with the overall efficacy.There was no statistically significant difference between 1 month and 3 months (P>0.05).Conclusions Carbon dioxide fractional laser is an effective and safe approach to treat syringoma with minimized side effects.