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Background A xenograft consisting of equine collagen coated with human fibrinogen and thrombin (TachoSil; Baxter, CA) has recently been introduced in grafting procedures for Peyronie’s disease (PD). Aim To describe the results of a multicenter prospective registry on patients with PD undergoing plaque incision or and grafting (PIG) or plaque excision and grafting (PEG) with collagen fleece TachoSil, to evaluate the efficacy and safety of this procedure. Methods A prospective non-controlled multicenter study of patients with PD was performed between May 2016 and March 2018. Patients from 10 centers with stable PD for at least 3 months, difficulties in sexual intercourse, normal erectile function with or without pharmacological treatment, curvature >45°, and/or penile shortening and/or complex deformities were included. All patients underwent PIG/PEG with collagen fleece TachoSil. Outcomes The main outcome measure of this study were penile curvature correction (intraoperative), penile shortening (intraoperative), erectile function with the 5-item version of the International Index of Erectile Function (IIEF-5) and the Erection Hardness Score, subjective patient outcomes with non-validated questionnaires, and complications. Results A total of 52 patients were enrolled in the study. The mean (SD) preoperative penile curvature was 72.8° (17.0). PIG was the preferred technique (80.8%). Intraoperatively, complete curvature correction was achieved in 92.3%, and no significant penile shortening was recorded in 80.8% of subjects. Subjective penile shortening was reported in 83.3% of patients at 6 months. No objective measurement of penile curvature and length was recorded during follow-up. No statistically significant difference from the baseline was found in IIEF-5 and Erection Hardness Score at 3 or at 6 months, although 16.7% of men experienced a worsening of IIEF-5 scores and 14.3% required de novo phosphodiesterase type 5 inhibitor use. 6 months after surgery, 78.5% of men were satisfied with intervention. Swelling and ecchymosis/hematoma were the most common perioperative complications (40.4%). 2 cases (3.8%) of wound infection were recorded. At 6 months, 35.7% of patients reported mild penile hypesthesia. Clinical implications Our results confirm the high success rate of grafting with TachoSil, and the surgeon perceived low percentage of penile shortening. Strength & Limitations This is the first multicentre study on patients with PD undergoing grafting with TachoSil without concomitant placement of penile prosthesis. The main limitations are the short follow-up and the relatively small sample size. Conclusion Grafting with TachoSil after PIG/PEG in patients with PD is an effective and safe procedure. Among the main advantages of this technique, there are ease of use of the graft and reduced operative time.