The purpose of this study is to determine if a procedure called Endoscopic Retrograde CholangioPancreatography (ERCP) with sphincterotomy reduces the risk of pancreatitis or the number of recurrent pancreatitis episodes in patients with pancreas divisum. ERCP with sphincterotomy is a procedure where doctors used a combination of x-rays and an endoscope (a long flexible lighted tube) to find the opening of the duct where fluid drains out of the pancreas. People who have been diagnosed with pancreas divisum, have had at least two episodes of pancreatitis, and are candidates for the ERCP with sphincterotomy procedure may be eligible to participate. Participants will be will be randomly assigned to either have the ERCP with sphincterotomy procedure, or to have a "sham" procedure. Participants will have follow up visits 30 days after the procedure, 6 months after the procedure, and continuing every 6 months until a maximum follow-up period of 48 months.

This is a sham-controlled, single blinded with a blinded outcome assessment, multi-center, randomized clinical trial of endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla endoscopic sphincterotomy (miES) for the treatment of recurrent acute pancreatitis (RAP) with pancreas divisum. ERCP with miES is often offered in clinical practice to patients with RAP, pancreas divisum, and no other clear risk factors for their acute pancreatitis episodes. The hypothesis is that obstruction at the level of the minor papilla is one cause of RAP in pancreas divisum; miES will relieve the obstruction, thereby reducing the risk of a recurrent attack(s) of acute pancreatitis. The trial requires a total sample size of approximately 234 subjects, and a planned enrollment period of approximately 3.5 years with total planned study duration of 5 years (minimum follow-up of 6 months, maximum follow-up of 48 months).

Inclusion Criteria:

1. Patient must consent to be in the study and must have signed and dated an approved consent form.

2. >18 years

3. Two or more episodes of acute pancreatitis, with each episode meeting two of the following three criteria:

   • abdominal pain consistent with acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back)
   • serum lipase activity (or amylase activity) at least three times greater than the upper limit of normal
   • characteristic findings of acute pancreatitis on CECT, MRI or transabdominal ultrasonography

4. At least one episode of acute pancreatitis within 24 months of enrollment

5. Pancreas divisum confirmed by prior MRCP that is reviewed by an abdominal radiologist at the recruiting site.

6. By physician assessment, there is no certain explanation for recurrent acute pancreatitis.

7. Subjects must be able to fully understand and participate in all aspects of the study, including completion of questionnaires and telephone interviews, in the opinion of the clinical investigator

Exclusion Criteria:

1. Prior minor papilla therapy (endoscopic or surgical)
2. Calcific chronic pancreatitis, defined as parenchymal or ductal calcifications identified on computed tomography or magnetic resonance imaging scan that is reviewed by an expert radiologist at the recruiting site.
3. Main pancreatic duct stricture*
4. Presence of a structural etiology for acute pancreatitis, such as anomalous pancreatobiliary union, periampullary mass, or pancreatic mass lesion on imaging*
5. Presence of a local complication from acute pancreatitis which requires pancreatogram
6. Regular use of opioid medication for abdominal pain for the past three months
7. Medication as the etiology for acute pancreatitis by physician assessment
8. TWEAK score ≥ 4

In addition to the participant and the investigator assessing outcomes, study coordinators involved in collecting outcomes data will be masked to the treatment assignment.