Background Common bile duct (CBD) cannulation is a critical step in endoscopic retrograde cholangiopancreatography (ERCP), essential for diagnosing and treating biliary and pancreatic disorders. Objective The objective of this study is to compare the success rates of common bile duct (CBD) cannulation performed using various techniques. Methods A prospective study was conducted in which patients were randomly assigned to receive cannulation with either a standard catheter or a sphincterotome (standard or wire-guided). Multivariate models were used to identify key factors influencing the success rates of both initial and selective cannulation, along with the number of attempts and the time required to achieve selective cannulation. Results A total of 83 patients were initially evaluated, 47 were included in the study, with most undergoing ERCP for suspected bile duct stones. Patients were randomized to receive either a standard catheter or a standard/wire-guided sphincterotome for selective common bile duct cannulation. The sphincterotome group had a significantly higher initial cannulation success rate (97% vs. 67%, p = 0.009) and required fewer attempts and less time to achieve cannulation (p = 0.0001). Multivariate analysis identified the initial choice of the catheter as the key independent predictor of both the time and number of attempts needed for successful cannulation. Conclusion The standard/wire-guided sphincterotome outperformed the standard catheter in the initial attempt at common bile duct cannulation. The number of attempts required could have clinical implications for the risk of post-ERCP pancreatitis, highlighting the need for further research.