Abstract Introduction Peyronie's disease (PD) is a common condition which results in penile curvature making sexual intercourse difficult or impossible. Collagenase clostridium histolyticum (CCH) is the first licensed drug for the treatment of PD and is indicated in patients with palpable plaque and curvature deformity of at least 30° of curvature. Objective To evaluate the results of a group composed of 2200 patients treated with clostridium histolyticum collagenase from December 2016 to March 2023, in a single European center. Methods We proceeded to review the database of 2200 patients diagnosed with PD with the aim of evaluating the efficacy of the treatment, number of injections performed, side effects in the short and long term, comorbidities of the patients, use of anticoagulants, onset of the disease, repercussions on the partner, satisfaction with the result; both objectively with calculation of curvature improvement, and subjectively, with improvement of the patient's clinical picture. All the patients performed a self-photograph in erection before the treatment and at the end of the same, with calculation of the curvature using a goniometer to evaluate the objective improvement, they also answered a simple question on the improvement (YES-NO) for the subjective picture. Patients were classified as mild if < 30° degrees; moderate 30°-60° and severe if > 60° according to Kelami's classification. 55 The protocol we followed was that of 3 applications 36–60 days apart according to the Ralph protocol used in Europe with the possibility of performing 1 to 3 treatments based on the efficacy of the drug, adverse events and costs. Results We evaluated 2200 patients of mean age 54.3 (range 15–77), with partners of mean age 49.8 (range 18–67). Of these, 154 (7%) had curvature less than 30°, 1320 (62%) had curvature between 30–60 degrees, and 726 (33%) had curvature >60°.As regards the stage of the disease, 726 (33%) had an active disease that arose for < 12 months, the remaining 1474 (67%) had a disease in the stabilized phase > 12 months. As regards comorbidities, 1276 patients (58%) were without any, 308 (14%) were hypertensive in pharmacological therapy with 1–3 drugs, 110 (5%) diabetic in therapy; of these 418 patients, 65 (2.95%) had both pathologies; 44 patients (2%) had Dupuytren's disease; 110 (5%) benign prostatic hypertrophy; 88 (4%) prior history of penile trauma with hematoma; 66 (3%) prior congenital curved penis. A further 6% other pathologies. Regarding the outcomes, 1474 (67%) showed an improvement in curvature of 10–30 degrees; 325 (14.7%) despite not having had an improvement in curvature reported that they were satisfied with the treatment. 1799 (81.8%) patients were satisfied with the treatment against 401 (18.2%) in which there was no subjective or objective improvement. With regard to complications, 946 (43%) presented slight edema/hematoma that resolved itself in the 48 hours following treatment, in 25 (1.1%) patients a major hematoma was reported which resolved in 1–2 weeks, in 1 single patient, equal at 0.04%, initial allergic reaction resolved with medical therapy based on cortisone and antihistamines (the patient reported a history of drug allergies). Conclusions Peyronie's disease remains a syndrome yet to be classified as the exact etiology and pathophysiology is not known. The only treatment approved by both the FDA and the EMA is CCH which can improve curvature by about 20 degrees. In expert hands, the possible complications are exclusively the hematoma. The satisfaction of the patient and of the partner is extremely high, the cost and the difficult availability outside the USA remain the two weak points of the treatment. These data, which certainly represent the largest case series in the world, highlight the need to re-evaluate all the literature on the subject of comorbidities and confirm that collagenase is today the gold standard of treatment which probably cannot follow pre-established therapeutic schemes, but the therapy must be set on the basis single patient. Disclosure No.