Objective To explore the application effect of CO2 fractional laser with comprehensive scanning mode in the treatment of patients with atrophic acne scars. Methods From June 2021 to June 2023, 68 patients with atrophic acne scars admitted to the Department of Dermatology, Chenzhou 198th Hospital were selected as the research objects. According to the random number table method, they were divided into control group and experimental group, with 34 patients in each group. The control group was treated with CO2 fractional laser with conventional scanning mode, and the experimental group was treated with CO2 fractional laser with comprehensive scanning mode. The scab formation time, erythema time, clinical efficacy, pain level, scar condition and adverse reactions were compared between the two groups. Results There was no significant difference in scab formation time and erythema time between the two groups (P >0.05). The total effective rate of treatment in the experimental group was 97.06%, which was higher than 79.41% in the control group (P <0.05). The VAS score of the experimental group at the first, second and third treatment were lower than that of the control group (P <0.05). The VSS score of the experimental group at the first, second and third treatment were lower than that of the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion CO2 fractional laser with comprehensive scanning mode has a good effect in the treatment of atrophic acne scars. It will not prolong the time of scab formation and erythema, and can effectively improve the total effective rate of treatment, help to reduce the pain level of patients, improve scar conditions, and promote recovery.