Background/aims: Oxygen free radicals play an important role in acute pancreatitis. Pantoprazole as a proton pump inhibitor (PPI) has pancreatic anti-secretory effect and a pronounced inhibitory reactivity towards hydroxyl radicals. The objective of the study was to investigate the effect of pantoprazole on the course of acute pancreatitis., Methods: We conducted a prospective randomized trial involving 40 patients with acute pancreatitis. Patients were divided into two groups. One group received PPI and the other group did not receive PPI. In the PPI group, patients received pantoprazole 40 mg intravenously twice a day for fasting time, and then 40 mg orally twice a day until discharge., Results: There were no significant differences in baseline characteristics and laboratory markers between two groups. In the pantoprazole group, mean hospital stay was 7.4 days, time to start oral intake was 69.0 hours, and time to pain relief was 59.7 hours. Acute physiology and chronic health evaluation (APACHE) II score was 3.15 at admission day and 2.35 at discharge. On the other hand, in the non-pantoprazole group, mean hospital stay was 7.6 days, time taken to start oral intake was 71.4 hours, and time taken to pain relief was 61.8 hours. APACHE II score was 4.4 at admission and 2.85 at discharge. However, there were no significant differences between two groups., Conclusions: Treatment with pantoprazole did not have influence on the clinical course of acute pancreatitis. But, considering it was a pilot study, large scale prospective trials will be needed.