OBJECTIVE We have investigated outcomes of women presenting with recurrent high-grade vaginal intra-epithelial neoplasia. METHODS Data of consecutive women diagnosed with recurrent high-grade vaginal intra-epithelial neoplasia after primary treatment(s) were retrieved. Risk of developing new recurrence over the time was assessed using Kaplan-Meier and Cox models. RESULTS Data of 117 women were available for the analysis. At primary diagnosis, 41 (35%), 4 (3.4%) and 72 (61.6%) patients had had laser, pure surgical and medical treatments, respectively. Secondary treatments included: laser ablation and medical treatment in 95 (81.2%) and 22 (18.8%) cases, respectively. After a mean (standard deviation) follow-up of 72.3 (±39.5) months, 37 (31.6%) out of the entire cohort of 117 patients developed a second recurrence. Median time to recurrence was 20 (range,5-42) months. Patients with recurrent high-grade vaginal intra-epithelial neoplasia undergoing medical treatments were at higher risk of developing a second recurrence in comparison to women having laser treatment (p=0.013, log-rank test). After we corrected our results for type of treatment used for recurrent disease, we observed that the execution of primary laser treatment was independently associated with a lower risk of developing new recurrences (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.21-0.99; p=0.050). The other variable that is independently associated with a new recurrence is the persistent infection from HPV16 or 18 (HR=3.87; 95% CI=1.15-13.0; p=0.028). CONCLUSIONS Patients with recurrent high-grade vaginal intra-epithelial neoplasia are at high risk of developing new recurrences. Our data underline that the choice of primary treatment might have an impact of further outcomes.