OBJECTIVE Experimental and clinical studies demonstrated that probiotics containing lactobacilli significantly improve the outcome of acute pancreatitis. In a prospective, randomized, double-blinded study the role of "Synbiotic 2000", a new synbiotic composition with high colony forming unit (CFU) was evaluated in the treatment of severe acute pancreatitis. METHODS Patients with severe acute pancreatitis were randomized into two groups. Nasojejunal feeding was commenced within 24 hours after admission in both groups and continued for at least seven days. The first group of patients received four different lactobacilli preparations with 1010 CFU, respectively, and prebiotics containing four bioactive fibers (inulin, beta-glucan, resistant starch and pectin) in addition. Patients in the second (control) group received only prebiotics. RESULTS 62 patients with severe acute pancreatitis completed the study. Altogether 8 patients died. Lower incidence of multiorgan failure (MOF), septic complications and mortality were detected in the first group compared to the control, but the differences were not significant statistically. The total incidence of systemic inflammatory response syndrome (SIRS) and MOF were significantly different between the two groups (8 vs. 14; p < 0.05). Furthermore, the number patients recovering with complications were significantly less in the first group receiving modern synbiotic therapy compared to the control (p < 0.05). Finally, lower rate of late (over 48 hours) organ failure was detected in the first versus the control group (3.0% vs. 17.2%). CONCLUSIONS The results suggest that early nasojejunal feeding with synbiotics may prevent organ dysfunctions in the late phase of severe acute pancreatitis. In addition, the data also indicate that the infection of pancreatic necrosis may be associated with early phase organ failure.