To explore the application effect of ultra-pulsed CO2 fractional laser combined with microneedle therapy in patients with atrophic acne scar. Methods Sixty patients with atrophic acne scars admitted to our hospital from January 2021 to October 2022 were selected as the research objects. They were divided into control group and observation group by random number table method, with 30 patients in each group. The control group was treated with ultra-pulsed CO2 fractional laser, and the observation group was treated with ultra-pulsed CO2 fractional laser combined with microneedle therapy. The clinical efficacy, quality of life and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 93.33%, which was higher than 73.33% in the control group (P <0.05). After treatment, the scores of selfperception, emotional function, acne symptoms and social function in the two groups were higher than those before treatment, and those in the observation group were higher than the control group (P <0.05). The incidence of adverse reactions in the observation group was 10.00%, which was lower than 33.33% in the control group (P <0.05). Conclusion Ultra-pulsed CO2 fractiona laser combined with microneedle therapy is effective in the treatment of atrophic acne scar, which can effectively improve the quality of life of patients, with low incidence of adverse reactions and high safety.