Introduction: Roux-en-Y choledochojejunostomy and duct-to-duct (D-D) anastomosis are biliary reconstruction methods for liver transplantation. However, there is a controversy over which method produces better results. We have compared the outcome of D-D anastomosis vs. Roux-en-Y hepaticojejunostomy in patients with primary sclerosing cholangitis who had undergone liver transplant in Shiraz Organ Transplant Center. Materials: The medical records of 405 patients with primary sclerosing cholangitis (PSC) who had undergone liver transplant from 1996 to 2015 were reviewed. Patients were divided into two groups: Roux-en-Y group and D-D group. Morbidity, disease recurrence, and graft and patient survival rates were compared between the two groups. Results: Total of 143 patients underwent a D-D biliary reconstruction, and 260 patients had a Roux-en-Y loop. Biliary complication involved 4.2% of patients from the D-D group, and 3.9% from the Roux-en-Y group (P=.863). Actuarial 1-, 3-, and 5-year patient survival for D-D and Roux-en-Y group was 92%, 85%, and 74%; and 87%, 83%, and 79%, respectively (P=.384). The corresponding 1-, 3-, and 5-year probability of biliary complication was 97%, 95%, and 92%; and 98%, 97%, and 94%, respectively (P=.61). Conclusion: Duct-to-duct biliary reconstruction in liver transplantation for selected patients with PSC is a good alternative instead of Roux-en-Y biliary reconstruction.