OBJECTIVE: Our purpose was to profile patients with vaginal intraepithelial neoplasia, evaluate the response to treatment and define risk factors for persistence and progression. STUDY DESIGN: We reviewed records and histopathology slides of 94 patients with vaginal intraepithelial neoplasia diagnosed from 1977 to 1986. For 74 patients with follow-up, we evaluated risk factors by univariate and multivariate analyses. RESULTS: Sixty-four of 94 patients (68%) had prior or concurrent anogenital squamous neoplasia, including 21 with invasive and 43 with intraepithelial. Twenty-three had prior radiotherapy, 10 had anogenital neoplastic syndrome, and 11 were immunosuppressed. In 52 of 74 treated patients (70%), vaginal intraepithelial neoplasia went into remission after a single treatment. In 18 patients (70%) vaginal intraepithelial neoplasia went into remission after a single treatment. In 18 patients (24%) recurrent vaginal intraepithelial neoplasia went into remission after chemosurgery, upper vaginectomy, or other treatments; in 4 (5%) it progressed to invasion. Significant multivariate risk factors for persistence or progression were multifocal lesions and anogenital neoplastic syndrome but not vaginal intraepithelial neoplasia grade, associated cervical neoplasia, or immunosuppression. CONCLUSIONS: Although most vaginal intraepithelial neoplasia goes into remission after treatment, 5% of cases may progress from occult foci to invasion in spite of close follow-up.