Objectives.We examined the association between Helicobacter pylori infection and the incidence of diarrheal diseases. Methods. In a nested case-control study participants were sampled from cohorts of male Israeli soldiers aged 18-21 years, serving in field units and followed up for diarrheal diseases. Case patients (n = 177) were subjects who visited the base clinic because diarrhea and were positive for Shigella sonnei (n = 66), enterotoxigenic Escherichia coli (ETEC) (n = 31) or negative for bacterial pathogens (n = 80; diarrhea of unknown etiology). Controls (n = 418) were subjects who did not suffer from a diarrheal disease during the follow-up. They were matched to case patients by training unit and period. Serum samples were obtained from participants at the beginning of their field training and were tested for anti-H. pylori immunoglobulin (Ig) G and preexisting Shigella sonnei lipopolysaccharide IgG and IgA antibodies using enzyme-linked immunosorbent assay.Results.The proportion of H. pylori-infected subjects was significantly lower among case patients with infection of unknown etiology (36.3%) than among controls (56.0%) (adjusted odds ratio [OR], 0.43; 95% confidence interval [CI],. 24-.77; P =. 005). The proportion of H. pylori-infected subjects among case patients with S. sonnei shigellosis was also significantly lower than in the control group: 36.3% versus 56.0%. The association persisted after adjusting for sociodemographic variables and preexisting S. sonnei serum IgA antibodies (adjusted OR, 0.37; 95% CI,. 14-.95; P =. 03) and IgG antibodies (adjusted OR, 0.38; 95% CI,. 14-.99; P =. 04). The direction of the association between H. pylori infection and ETEC diarrhea was similar, albeit not statistically significant. Conclusions. Our findings suggest an active role of H. pylori in protection against diarrheal diseases.