Abstract: Objective To observe the efficacy, safety, recurrence rate of photodynamic therapy with topical application of 5-aminolevulinic acid (5-ALA) combined with recombinant human interferon α -2b gel in treatment of condyloma acuminatum. Methods One hundred and ninety-five patients with condyloma acuminatum were randomly divided into observation group (n=102) and control group (n=93). The two groups received photodynamic therapy with topical application of 5-aminolevulinic acid once a week for 3 times. Patients in observation group were treated with extra recombinant human interferon α -2b gel which was applied 2 cm away from the edge of the wart after topical ALA-PDT treatment. The cure rate, recurrence rate and side effects in two groups were observed. Results Follow up was done for 3 months after the 3 times treatment, the cure rate of observation group and control group was 95.10% and 87.10%, respectively. And the recurrence rate of two groups was 4.90% and 12.90%, respectively. There were statistically significant differences in cure rate and recurrence rate in two groups (P ＜ 0.05). The adverse event was generally mild to moderate. No severe side effects were observed. Conclusion Photodynamic therapy with topical application of 5-aminolevulinic acid combined with recombinant human interferon α -2b gel for urethral condyloma acuminatum is a safe, effective and reliable treatment with low recurrence rate and good tolerance.