We attempted to evaluate the therapeutic effect of trichloroacetic acid (TCA) for vaginal intraepithelial neoplasia (VaIN) after hysterectomy and to identify factors affecting persistence/recurrence. Twenty-eight post-hysterectomy patients with various grades of VaIN were enrolled in this study between January 2001 and December 2003. They were managed with intravaginal 50% TCA once weekly for 1-4 weeks, and all patients were followed up every 3 months for at least 1 year. Assessments by Papanicolaou smear and colposcopy were performed, as was biopsy when indicated during the follow-up period. Cox regression analysis was used to identify independent factors predicting persistence/recurrence. In 20 of 28 patients (71.4%) VaIN went into remission. Treatment success was observed in all 11 patients with VaIN I, whereas only 9 out of 17 patients (53%) with VaIN II/III went into remission (P = 0.009). Severity of VaIN was the only significant independent predictor of persistence/recurrence (odds ratio = 3.5; 95% confidence interval = 1.1, 11.6; P = 0.038). The treatment was well tolerated with no major side effects. Based on our findings, 50% TCA was a potential agent with minimal side effects for low-grade VaIN. Further prospective controlled study is warranted to verify our statements. However, as for high-grade lesions, further investigation with different TCA concentration is compelling.