AIMTo compare the cannulation success, biochemical profile, and complications of the papillary fistulotomy technique vs catheter and guidewire standard access.METHODSFrom July 2010 to May 2017, patients were prospectively randomized into two groups: Cannulation with a catheter and guidewire (Group I) and papillary fistulotomy (Group II). Amylase, lipase and C-reactive protein at T0, as well as 12 h and 24 h after endoscopic retrograde cholangiopancreatography, and complications (pancreatitis, bleeding, perforation) were recorded.RESULTSWe included 102 patients (66 females and 36 males, mean age 59.11 ± 18.7 years). Group I and Group II had 51 patients each. The successful cannulation rates were 76.5% and 100%, respectively (P = 0.0002). Twelve patients (23.5%) in Group I had a difficult cannulation and underwent fistulotomy, which led to successful secondary biliary access (Failure Group). The complication rate was 13.7% (2 perforations and 5 mild pancreatitis) vs 2.0% (1 patient with perforation and pancreatitis) in Groups I and II, respectively (P = 0.0597).CONCLUSIONPapillary fistulotomy was more effective than guidewire cannulation, and it was associated with a lower profile of amylase and lipase. Complications were similar in both groups.