Background: Managing acute abdominal pain in the large and growing population of Roux-en-Y gastric bypass (RYGB)–operated patients poses a challenge to general surgeons, because of diagnostic limitations and the risk of internal herniation. Objective: To investigate the diagnoses, management, and outcome of RYGB patients admitted for acute abdominal pain. Setting: University Hospital, Sweden. Methods: Prospective inclusion of 280 consecutive RYGB patients admitted for acute abdominal pain between April 2012 and June 2015. Readmissions, surgical procedures, and overall mortality were recorded until October 2018. Medical records were retrospectively reviewed for anthropometric measures, medical history, time from RYGB surgery, and previous closure of mesenteric gaps. Admissions were separated into early (≤30 d) or late (>30 d) after RYGB. Procedures performed were categorized as follows: RYGB complication, other surgery, or unremarkable laparoscopy. Patients discharged with diagnosis of unspecified abdominal pain were separately analyzed. Diagnostic investigations, bariatric competency, on call surgery, surgical complications, and length of stay were registered. Results: In late admissions, the cause of the abdominal complaints remained unexplained in 127 of 262 (48%) patients despite 95 abdominal computed tomographies and 28 diagnostic laparoscopies. Emergency surgery was performed in 128 of 262 (49%) patients. RYGB complications (n = 66), mainly internal herniation (n = 42), were >2 times more frequent than other surgical procedures (n = 32), such as cholecystectomies (n = 23). Internal herniation could occur at any time interval from RYGB surgery and regardless of previously closed mesenteric gaps. Conclusion: Better tools for evaluation of acute abdominal pain in RYGB patients are needed to reduce the number of unremarkable laparoscopies and admissions of patients with unspecified abdominal pain.