Objective To explore the efficacy and safety of intralesional injection of triamcinolone acetonide injection combined with CO? fractional laser in patients with keloid. Methods A total of 180 patients with keloid admitted to Yili Friendship Hospital from January 2023 to June 2024 were selected and divided into group A and group B by the random number table method, with 90 patients in each group. Group A was given intralesional injection of triamcinolone acetonide injection, and group B was given intralesional injection of triamcinolone acetonide injection combined with CO? fractional laser treatment. The aesthetic effect, clinical efficacy, adverse reaction rate and recurrence rate were compared between the two groups. Results After treatment, the scores of scar thickness, softness, vascular distribution, color, pruritus and pain in the two groups were lower than those before treatment, and those in group B was lower than those in group A (P <0.05). The total effective rate in the group B (97.78%) was higher than that in group A (81.11%) (P <0.05). There was no significant difference in the incidence of adverse reactions between group A and group B ( P >0.05). The recurrence rate of group B (3.33%) was lower than that of group A (16.67%) (P <0.05). Conclusion Intralesional injection of triamcinolone acetonide injection combined with CO? fractional laser in the treatment of keloid has good aesthetic effect, which can effectively improve scar symptoms, does not increase the incidence of adverse reactions, and has a low recurrence rate after treatment, with good efficacy and safety.