The aim of the present study was to evaluate the role of sulglycotide, a molecule with gastroprotective properties, in monotherapy and in association with H2-antagonists in the maintenance treatment of duodenal ulcer. The study was performed using a fully randomized experimental design. Following endoscopic confirmation, 626 patients with healed duodenal ulcer were treated for 6 months with sulglycotide 200 mg tid (293 patients) or sulglycotide + H2-antagonists (333 patients). After 2, 4 and 6 months patients underwent a clinical control whereas an endoscopic control was performed after 6 months. The cumulative percentage of recidivation was 3.6% in the sulglycotide + H2-antagonist treated group, whereas the group treated with sulglycotide alone showed a recidivation rate of 15.4% (p < 0.001). These findings suggest the utility of combined sulglycotide and H2-antagonist treatment in the maintenance therapy for duodenal ulcer.