To determine the natural history of chronic pancreatitis (CP), we retrospectively studied 193 consecutive patients who had at least one hospitalization for the control of pain or a complication of CP by examining the hospital records and by using a standard questionnaire. Alcohol (66%) was the major cause of CP and the cause was unknown in 21%. Pain was the presenting symptom in 93%. Pancreatic calcification was observed in 41% (alcoholic 54% vs. nonalcoholic 19%; OR = 6.7, CI = 2.7, 14.3; p < 0.0001). Diabetes (28%), malabsorption (16%), pseudocysts (21%) and pancreatic (3%) or extrapancreatic malignancy (5%) were the main complications. 43% had surgical intervention for pain relief, 10% had either endoscopic sphincterotomy or surgical sphincteroplasty and 16% had surgery for complications. Surgical or endoscopic intervention was more commonly performed in nonalcoholics compared with alcoholics (OR = 12.8, CI = 3.6, 53.9; p < 0.0001). However, if sphincterotomy and sphincteroplasty were excluded, the total number of surgical procedures for pain relief was similar in both groups. Complete follow-up information was available in 107 patients with a mean duration of follow-up of 10 years (range, 1-28 years); 27 patients died during the follow-up; 5, 10 and 15 year mortality was 14%, 18% and 20% respectively. The mortality was significantly higher in patients with alcoholic CP than in nonalcoholic CP (35% vs. 10%; OR = 1.4, 18.7; p = 0.005). Of the 80 patients who were alive and had complete long-term follow-up, pain improved in 62 patients, remained unchanged in 17 and worsened in one. Pain improved in 34 of 41 (83%) patients who had surgical intervention for pain, 7 of 9 patients (78%) who had surgery for complications, 4 of 7 (57%) who had sphincter ablation and 17 of 23 patients (74%) who had nonprocedural treatment. Long-term pain relief was similar in patients with alcoholic and nonalcoholic pancreatitis.