PurposeVulvar lichen sclerosus (LS) is a chronic, progressive, autoimmune dermatologic condition that causes cutaneous changes accompanied by pruritus and pain. There remains a small population with vulvar LS refractory to topical corticosteroids. Injection of platelet-rich plasma (PRP) has been reported to have positive effects on tissue repair. The aim of this pilot study was to evaluate changes in symptom scores during and after PRP vulvar infiltration.MethodsThree PRP infiltrations were administered to 28 female postmenopausal patients with biopsy-proved LS with unsatisfactory response to steroid therapy. Change in score according to the Clinical Scoring System for Vulvar Lichen Sclerosus (CSS) was measured on six occasions over the course of a year. We used growth curve modeling to measure change over the period of the study.ResultsWomen in our study experienced a statistically significant improvement in auto-assessed symptoms of vulvar lichen sclerosus, and this improvement appears to be maintained throughout the monitoring year.ConclusionPlatelet-rich plasma may have a role in symptom relief in certain cases of patients with LS that do not respond to first-line therapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00403-023-02529-1.