Objective To analyze the effect of the triple therapy system consisting of carbon dioxide (CO2) laser, recombinant human interferon-α1b (rhIFN-α1b) and 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on lesion wart area in patients with recurrent condyloma acuminatum (CA). Methods A total of 50 patients with recurrent CA admitted to the Department of Dermatology and Medical Aesthetics, People’s Hospital of Pengshui Miao and Tujia Autonomous County from January to August 2025 were selected as the research subjects, and they were divided into the control group and the observation group by the random number table method, with 25 patients in each group. The control group was treated with the dual therapy system of CO2 laser combined with rhIFN-α1b, and the observation group was treated with the triple therapy system of CO2 laser combined with rhIFN-α1b and ALA-PDT. The lesion wart area, clinical efffcacy, recurrence rate and adverse reaction rate were compared between the two groups. Results The lesion wart area of the observation group at 3 months after treatment was smaller than that of the control group (P<0.05). The total effective rate of the observation group (92.00%) was higher than that of the control group (68.00%) (P<0.05). The recurrence rate of the observation group was 8.00% (2/25), which was lower than 36.00% (9/25) of the control group (P<0.05). There was no statistically signiffcant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion For patients with recurrent CA, the therapeutic regimen of CO2 laser combined with rhIFN-α1b and ALA-PDT has favorable clinical effects, which can effectively reduce the recurrence risk and improve the lesion area, and has high safety, without increasing the risk of adverse reactions.