ObjectiveTo evaluate the clinical outcomes of vaginectomy and laser ablation for the treatment of vaginal high-grade squamous intraepithelial lesion (HSIL) patients who underwent previous hysterectomy for cervical HSIL or cancer. Study DesignThe clinicopathologic data and follow-up information of 167 post-hysterectomy vaginal HSIL patients who underwent laser ablation or vaginectomy were retrospectively reviewed from 2010 to 2018 at the Obstetrics and Gynecology Hospital of Fudan University. ResultsOf the 167 vaginal HSIL patients enrolled, 74 patients underwent vaginectomy, and 93 patients underwent laser ablation. At a median follow-up of 15 months, 13 (7.8 %) patients experienced progression to vaginal cancer, and 22 (13.2 %) patients had persistent/recurrent disease. Upon multivariate analysis, laser ablation (OR: 5.16, p = 0.02), cytology indicating HSIL (OR: 25.45, p = 0.00), and a shorter interval between previous hysterectomy and vaginal HSIL diagnosis (< 24 vs ≥ 24 months, OR: 0.10, p = 0.02) were associated with disease persistence/recurrence. In post-hysterectomy for cervical HSIL patients, the vaginectomy group had a significantly higher recurrence-free survival rate (RFS, 94.5 % vs 69.0 %, p = 0.00) and a similar progression-free survival rate (PFS, 96.4 % vs 91.4 %, p = 0.17) compared with the laser ablation group. Among post-hysterectomy for cervical cancer patients, RFS (89.5 % vs 65.7 %, p = 0.04) and PFS (100.0 % vs 82.9 %, p = 0.05) were both higher in the vaginectomy group than in the laser ablation group. ConclusionCompared with laser ablation, vaginectomy resulted in better clinical outcomes among vaginal HSIL patients who had undergone previous hysterectomy for cervical neoplasia.