Objective To determine whether surgical intervention prevents recurrent acute exacerbations in chronic pancreatitis (CP). Summary Background Data The primary goal of surgical intervention in the treatment of CP has been relief of chronic unrelenting abdominal pain. A subset of patients with CP have intermittent acute exacerbations, often with increasing frequency and often unrelated to ongoing ethanol abuse. Little data exist regarding the effectiveness of surgery to prevent acute attacks. Methods From 1985 to 1999, all patients identified with a diagnosis of CP were recruited to participate in an ongoing program of serial clinic visits and functional and clinical evaluations. Patients were offered surgery using standard criteria. Data were gathered regarding ethanol abuse, pain, narcotic use, and recurrent acute exacerbations requiring hospital admission before and after surgery. Patients were broadly categorized as having severe unrelenting pain alone (group 1), severe pain with intermittent acute exacerbations (group 2), and intermittent acute exacerbations only (group 3). Results Two hundred fifty-nine patients were recruited. One hundred eighty-five patients underwent 199 surgical procedures (124 modified Puestow procedure [LPJ], 29 distal pancreatectomies [DP], and 46 pancreatic head resections [PHR; 14 performed after failure of IPJ]). There were no deaths. The complication rate was 4% for LPJ, 15% for DP, and 27% for PHR. Ethanol abuse was causative in 238 patients (92%). Mean follow-up was 81 months. There were 104 patients in group 1 (86 who underwent surgery), 71 patients in group 2 (64 who underwent surgery), and 84 in group 3 (49 who underwent surgery). No patient without surgery had spontaneous resolution of symptoms. Postoperative pain relief (freedom from narcotic analgesics) was achieved in 153 of 185 patients (83%) overall: 106 of 124 (86%) for LPJ, 19 of 29 (67%) for DP, and 42 of 46 (91%) for PHR. The mean rate of acute exacerbations was 6.3 +/- 2.1 events per year before surgery in group 2 and 7.8 +/- 1.8 events per year in group 3. After surgery, no acute exacerbations occurred in 42 of 64 (66%) group 2 patients and in 40 of 49 (82%) group 3 patients. The mean number of episodes of acute exacerbation after surgery was 1.6 +/- 2.3 events in group 2 and 1.1 +/- 1.9 events in group 3. Only four patients in group 2 and one patient in group 3 had an equal or increased frequency of attacks after surgery. Preventing attacks was most effective with IPJ (58/64, 91%) and least effective for DP (6/18, 33%). Conclusions Surgical intervention prevents recurrent acute exacerbations. The overall frequency of events was reduced in nearly ail patients. Therefore, surgical intervention is indicated in patients with CP whose disease is characterized by recurrent acute exacerbations.