Background: The standard biliary cannulation technique has been reported to fail in approximately 5– 20% of cases so, several supplementary techniques have been recommended to facilitate access to the common bile duct (CBD); Double-guidewire technique (DGT) and transpancreaticsphincterotomy (TPS) are effective method in cases of standard biliary cannulation failure. Objective: To compare the outcomes between DGT and TPS in patients with difficult biliary cannulation regarding the procedure duration, success rate and complications. Patients and Methods: This was a randomized study conducted in Al-Hussein University Hospital, Endoscopy Unit in the period between May, 2016 to October, 2017. A total of 40 patients, who bile duct cannulation was not possible and selective pancreatic duct cannulation was achieved were randomized into DGT (n = 19) and TPS (n = 21) groups. DGT or TPS was done for selective biliary cannulation. We measured the technical success rates of biliary cannulation, median cannulation time, and procedure related complications. Results: The distribution of patients after randomization was balanced, and both groups were comparable in baseline characteristics. There was no significant difference between both groups regarding age and sex distribution, clinical presentation, laboratory findings and sonographic findings. Successful cannulation rate and mean cannulation times in DGT and TPS groups were 94.7% vs 95.2% and 20.1 ± 8.7min vs 21.5 ± 7.8min, P = 0.602, respectively. There was no significant difference between the two groups. Conclusion: When free bile duct cannulation was difficult and selective pancreatic duct cannulation was achieved, DGT and TPS facilitated biliary cannulation and showed similar success rates. However, post-procedure pancreatitis and Cholangitis were significantly higher in the DGT group.