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Aim There are few types of drugs that can be used in the active phase of Peyronie’s disease. Methylprednisolone is a corticosteroid with a strong anti-inflammatory effect. In this study, we aimed to evaluate the effect of intralesional low dose methylprednisolone treatment on patients in the active phase of Peyronie’s disease. Patients and Methods Forty-eight patients suffering from Peyronie’s disease active phase symptoms were included in the study. Methylprednisolone was administered intralesionally for 8 weeks, once per week, at a dose of 40 mg. The injection was applied into the plaques, which causes maximum curvature. Patients were evaluated before and after treatment for plaque size, angle of curvature, and erectile dysfunction according to the International Index of Erectile Function-5 and Peyronie’s Disease Questionnaire. Results The mean age of the patients was 61.1 (43-78) years. Mean duration of the symptoms was 3.4 (0-9) months. The average plaque size before treatment was 13.6 mm (7.1-16.8) and after treatment, this value decreased to 10.8 mm (4.3-14.6) (p:0.025). The average scores of Peyronie’s Disease Questionnaire elements; symptom severity, penile pain and bother/discomfort were 12.3, 19.1 and 6.2, respectively before the treatment. These scores were decreased to 8.9, 9.6 and 4.4, respectively after treatment. All subgroups of Peyronie’s Disease Questionnaire scores were significantly improved after treatment (p:0.001, p<0.001, p:0.045, respectively). No adverse events were observed during or after treatment. Conclusion In order to recover the symptoms and signs, new and easily accessible drugs are required for use in the acute period of Peyronie’s disease. In this context, treatment with intralesional low dose methylprednisolone in acute phase Peyronie’s Disease is a promising and safe treatment option.