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Adult vulvar lichen sclerosis (VLS) may be complicated by loss of vulvar structure and vulvar carcinoma. There is a lack of evidence as to the ideal method to maintain long-term remission and prevent complications.To determine whether long-term preventive topical corticosteroid (TCS) treatment of VLS, with a target outcome of induction and maintenance of normal skin texture and color, reduces the risk of vulvar carcinoma, relieves symptoms, improves function, and preserves vulvar architecture, and to evaluate the adverse effects of treatment.A prospective longitudinal cohort study was conducted in 507 women with biopsy-proved VLS from January 2, 2008, through September 26, 2014, in the private practice of a dermatologist and a gynecologist in Sydney, Australia.Preventive treatment using TCSs of various potencies, adjusted to meet a target outcome of normal skin color and texture, with regular long-term follow-up by a dermatologist or gynecologist.Symptoms or signs of VLS, scarring, development of malignant neoplasms, and adverse effects.The mean age at presentation was 55.4 years (range, 18-86 years); duration of symptoms at presentation, 5.0 years (range, 0.1-40.0 years); and duration of follow-up, 4.7 years (range, 2.0-6.8 years). Remission was induced with a potent TCS, followed by regular preventive TCS treatment of a potency titrated to achieve the target outcome. Patients were followed up at least annually. A total of 150 patients (29.6%) did not carry out the advised treatment and were considered partially compliant. A total of 357 patients (70.4%) adhered to treatment instructions and were considered compliant. Biopsy-proved squamous cell carcinoma or vulvar intraepithelial neoplasia occurred during follow-up in 0 of the compliant patients vs 7 (4.7%) of the partially compliant patients (P < .001). Suppression of symptoms occurred in 333 (93.3%) compliant patients vs 87 (58.0%) partially compliant patients (P < .001). Adhesions and scarring occurred during follow-up in 12 (3.4%) compliant patients and 60 (40.0%) partially compliant patients (P < .001). Reversible TCS-induced cutaneous atrophy occurred in 4 (1.1%) compliant patients and 3 (2.0%) partially compliant patients.This prospective, single-center, longitudinal cohort study of adult patients with VLS suggests that individualized preventive TCS regimens that achieve objective normality of skin color and texture and are used by compliant patients who attend regular long-term follow-up visits may modify the course of the disease. There was a significant difference in symptom control, scarring, and occurrence of vulvar carcinoma between compliant and partially compliant patients. The adverse effects of TCSs were minimal.