Background: Although topical therapies are used to treat extramammary Paget’s disease (EMPD), reliable treatment outcomes and the effects of these therapies on subsequent surgical treatments are unclear. Objectives: To assess the clinical outcomes of topical treatment of EMPD and establish the treatment guidelines. Methods: Medical records of 166 patients diagnosed with EMPD were retrospectively reviewed. The recurrence rate was evaluated according to the previous use of topical agents. Results: Thirty-four patients (34/166, 20.5%) were initially treated topical agents, like imiquimod, 5-fluorouracil, and ingenol mebutate. Three patients (3/34, 8.8%) showed clinical response, while 31 patients required subsequent therapy owing to treatment failure. Analysis of the prognostic factors of recurrence in 166 patients revealed that initial topical treatment increased the hazard ratio (HR) in both univariate and multiple Cox proportional hazards models (HR=3.770, 95% confidence interval (CI)=1.768-8.037, p=0.001, and adjusted HR=3.144, 95% CI=1.363-7.250, p=0.007). Patients treated with topical agents showed significantly poorer 3-year recurrence-free survival than the non-treated group (66.3% vs 88.6 %, p<0.001). Conclusion: Topical treatment may be deleterious for some EMPD patients, thus, increasing the recurrence risk.