Objective To investigate the efficacy and safety of sequential therapy with pulsed dye laser (PDL) combined with ultra-pulsed CO2 fractional laser in patients with hypertrophic scars. Methods The clinical data of 60 patients with hypertrophic scars admitted to the Department of Dermatology and Venereology, the Eighth Affiliated Hospital of Southern Medical University from January 2019 to December 2025 were retrospectively analyzed. According to different treatment methods, they were divided into the control group and the observation group, with 30 patients in each group. The control group received ultra-pulsed CO2 fractional laser treatment, and the observation group received sequential therapy of PDL combined with ultra-pulsed CO2 fractional laser. The Vancouver Scar Scale (VSS) score, scar thickness, blood perfusion, Patient and Observer Scar Assessment Scale (POSAS) observer score and adverse reaction rate were compared between the two groups. Results At 3 months after treatment, the scores of each dimension and total score of VSS in the two groups were lower than those before treatment, and those in the observation group were lower than those in the control group (P <0.05). At 3 months after treatment, the scar thickness and blood perfusion of the two groups were lower than those before treatment,and those in the observation group were lower than those in the control group (P <0.05). At 3 months after treatment, the scores of each dimension and total observer score of POSAS in the two groups were lower than those before treatment, and those in the observation group were lower than those in the control group (P <0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion Sequential therapy of PDL combined with ultra-pulsed CO2 fractional laser can synergistically improve the appearance and tissue structure of hypertrophic scars, reduce scar thickness and inhibit pathological blood supply, bringing better comprehensive improvement of scars. It has comparable safety to single laser therapy and possesses favorable clinical application value.