Purpose Lichen sclerosus (LS) is a chronic inflammatory skin condition that frequently involves the anogenital region. Ongoing research is focused on finding more effective treatments for tissue repair and reducing symptoms. The aim of this study is to evaluate the effectiveness of platelet-rich plasma (PRP) local injections in penile LS. Methods Forty-five male patients affected by penile LS underwent injections of autologous PRP in the affected skin areas. Age at diagnosis and at first treatment, number of treatments, clinical conditions (phimosis, splitting, inflammation, synechiae, meatus stenosis), symptoms (pain, burning, itching), and functional impairment were considered. Treatment efficacy was also evaluated through the Investigator's Global Assessment (IGA) on a six-point Likert scale and the Dermatology Life Quality Index (DLQI). Results The patient age at LS diagnosis was 36.20 +/- 9.19 years, while the mean age at the first PRP treatment was 42.96 +/- 11.32 years (p < 0.001). The number of treatments/patient ranged from 2 to 10. The follow-up was 17.60 +/- 5.63 months. After PRP injections, it was observed in all patients a significant improvement in clinical conditions, with reduction/disappearance of symptoms. Topical steroid therapy, interrupted before PRP treatment, was not restarted by any patient. Only one patient underwent a later circumcision procedure. Both IGA scale and DLQI score showed a significant difference (p < 0.001) before and after PRP treatment. Conclusions PRP treatment in penile LS seems to be helpful to regenerate scarring, reduce symptoms, and improve patient quality of life. Further studies are necessary to evaluate long-term results.