BACKGROUND Primary sclerosing cholangitis (PSC), comprising 5-15% of European liver transplantation (LT) cases, poses a significant challenge due to the risk of post-transplant disease recurrence (rPSC). This single-center study aimed to determine the rPSC rate and long-term post-LT outcomes in PSC patients and to identify potentially modifiable risk factors of rPSC. METHODS All PSC patients receiving LT at Padua Hospital from 1993 to 2021 were included. Recipient data were collected pre-LT, at LT, and during the follow-up. Donor and LT features were recorded. The rPSC rate was assessed according to Mayo Clinic criteria. Patient and graft survival were reported. RESULTS Thirty-three patients were included. The main indication of LT was decompensated cirrhosis (70%). Nine patients (27%) developed rPSC during a median follow-up of 59 months (45-72). A longer cold ischemia time (p = 0.026), donor female gender (p = 0.049), inflammatory bowel disease reactivation (IBD) post LT (p = 0.005) and hepaticojejunostomy (p = 0.019) were associated with a higher risk of rPSC. Graft and patient survival at 1, 5 and 10 years post LT, 94%, 86%, 74% and 97%, 89%, 77% respectively, were not affected by rPSC development. CONCLUSIONS Specific donor and surgical features might increase the risk of rPSC. Identifying predictive factors for rPSC to prevent graft loss is challenging but could lead to a more personalized organ allocation and follow-up in PSC transplanted patients. IBD reactivation might have a pathogenic role in rPSC. In our single-center experience, rPSC did not affect patient and graft survival.