Background and purpose: Mid-size sphincterotomy associated with large balloon dilation is an alternative to wide sphincterotomy to remove complex lithiases. However, which of the two techniques is most effective remains unclear. Hence, we conducted this study to compare both methods prospectively.Method: Since January 2012 until March 2014, 133 consecutive patients with complex stones were included. Group A underwent mid-size sphincterotomy associated with large balloon dilation and group B underwent wide sphincterotomy alone. Success rates were assessed for: Extraction of stones, ductal patency rate, the use of mechanical lithotripsy, dose, time and dose per radioscopy area as well as procedure-related complications.Results: Group A comprised 44 patients and group B comprised 69 patients. Overall success rate for extraction was 86.4% in group A and 70% in group B (p = 0.069). In giant lithiasis, effective extraction was 89.3% in group A and 58.6% in group B (p = 0.019). Use of mechanical lithotripsy was 15.9% and 30.4%, respectively (p = 0.142). Total radiotherapy dose was 39.8 mGy vs. 26.2 mGy, respectively (p = 0.134). Complications occurred in 6.8% and 5.5% of the procedures in each group, without significant differences among them (p = 0.856).Conclusion: Sphincterotomy plus large balloon dilation is more effective and equally safe than conventional sphincterotomy for the management of giant main bile duct lithiasis.