Introduction: Post-ERCP complications increase with repeated attempts at cannulation. We aimed to evaluate a number of advanced biliary cannulation techniques when standard approach fails. Methods: One thousand four hundred fifty-four consecutive patients underwent ERCP between May 2010 and July 2013 at our institution; their medical records were evaluated for demographic data, procedure indication, biliary cannulation technique used, cannulation success rate, and complications. Guidewire-assisted (GA) cannulation with no contrast injection until deep biliary cannulation was considered a standard technique. Double wire-guided (DWG) cannulation, transeptal papillary septotomy (TPS), and/or needle knife sphincterotomy (NKS) were considered advanced biliary cannulation techniques. In DWG cannulation, the bile duct is cannulated alongside a wire placed in the pancreatic duct (PD), using PD wire as a guide. In TPS-assisted biliary cannulation, a partial septotomy is performed after sphinctertome is introduced into the common channel of the papilla. Sphinctertome is then reintroduced and GA cannulation reattempted. A stepwise approach was applied: when standard technique failed, DWG cannulation was usually attempted first if PD wire was in place; if that failed, TPS or NKS was performed. Alternatively, TPS or NKS were performed alone. Results: The overall biliary cannulation success rate was 99.2% (1442/1454). Advanced techniques were used in 10% (150/1454) cases, with a 92% (138/150) success rate. Alone DWG technique was used in 69/150, TPS alone in 18/150, and NKS alone in 41/150; multiple techniques were used in 22/150. Overall DWG technique was applied in 90/150 procedures. Most common indication for ERCP requiring advanced techniques was jaundice secondary to stone disease or malignancy; average age was 50 years; 995/459 were female/male. DWG cannulation was successful in 76% (68/90). TPS was then used in 17/22 cases where DWG technique failed, and resulted in 94% (16/17) successful biliary cannulation. TPS alone was successful in 83% (15/18) cases; success rate of NKS alone was 85% (35/41). There was a trend towards increased use of TPS in the last 2 years reviewed. The overall rate of post-ERCP pancreatitis was 0.7% (6/1454), and all cases were mild. One case of pneumoperitoneum occurred after NKS and was treated conservatively. Of the 12 patients who failed advanced techniques on the first attempt, 4 were successfully cannulated with standard technique during repeat procedure. Conclusion: In our experience, the proposed stepwise approach to biliary cannulation using the double wire-guided technique is both safe and effective.