Objective: To evaluate the outcome of vaginal intraepithelial neoplasia (VaIN) treatment with CO2 laser vaporization in terms of local recurrence and progression to vaginal carcinoma. Additionally, the authors investigated the predictive factors for first recurrence. Materials and Methods: The medical records of all patients treated for VaIN with CO2 laser vaporization at Sant’Anna Hospital in Turin (1995-2012), were retrospectively reviewed. A univariate logistic model was applied to evaluate selected clinical features as predictive factors for recurrence. A multivariate logistic regression analysis was then carried out including significant risk factors after univariate analysis (p < 0.05). Results: The analysis included 285 out of 302 patients. Seventy-one (25%) women relapsed; of these 24 VaIN 1 (22%), 37 VaIN 2 (27%), and ten VaIN 3 (26%). The median time to the first recurrence was 5.2 months (1.4?127.8) for VaIN 1, 6.6 months (1?85.2) for VaIN 2, and 3.6 months (1.2?62) for VaIN 3. Sixty-one out of 71 patients were retreated with CO2 laser vaporization. At the last follow-up visit, 273 (96%) women were free from VaIN. No patients progressed to vaginal carcinoma. The multivariate model showed a higher risk of VaIN recurrence in the case of previous hysterectomy (HR 3.3, 95% CI 1.7?6.3, p < 0.001) and concomitant H-SIL on the Pap smear (HR 1.9, 95% CI 1.2?3.1, p = 0.008). Conclusion: CO2 laser vaporization is an effective low impact treatment for VaIN. Despite this, VaIN recur, in particular in cases of previous hysterectomy and concomitant H-SIL on the Pap smear. An intensive follow-up is proposed for women with a high risk of VaIN relapse.