BACKGROUND/OBJECTIVES: There is substantial evidence of superiority of enteral nutrition (EN) to parenteral nutrition in acute pancreatitis (AP) treatment, but few studies evaluated its effectiveness compared to no intervention. The objective of our trial was to compare the effects of EN to a nil-by-mouth (NBM) regimen in patients with AP. METHODS: Patients with AP were randomized to receive either EN via a nasojejunal tube initiated within 24 h of admission or no nutritional support. Systemic inflammatory response syndrome (SIRS) was assessed as the primary outcome. Secondary outcomes included mortality, organ failure, local complications, infected pancreatic necrosis, surgical interventions, length of hospital stay, adverse events and inflammatory response intensity. Outcomes were compared using Student's t-test and Mann- Whitney U test as appropriate. RESULTS: 214 patients were randomized in total, 107 to each group. SIRS occurrence was similar between groups, with 48 (45%) versus 51 (48%), respectively (RR 0.94 ; 95% CI 0.71-1.26). No significant reduction of persistent organ failure (RR 0.81 ; 95% CI 0.52-1.27) and mortality (RR 0.59 ; 95% CI 0.28-1.23) was present in the EN group. There were no significant differences in other outcomes between the groups. When analyzing the occurrence of SIRS and mortality in subgroup of patients with severe disease no significant differences were noted. CONCLUSION: Our results showed no significant reduction of persistent organ failure and mortality in patients with AP receiving early EN compared to patients treated with no nutritional support (NCT01965873).