Background: Children in the developing world acquire Helicobacter pylori infection soon after birth, and there is evidence that it plays a part in the development of persistent diarrhea through suppression of the gastric acid barrier and hence predisposing to small bowel bacterial overgrowth which may be responsible for the pathogenesis of the syndrome of diarrhea, malnutrition and growth failure. Aim: To determine the role of Helicobacter pylori infection as a cause of persistent diarrhea in Egyptian infants and children using PCR technology. Methods: Thirty pediatric patients with persistent diarrhea, together with fifteen age and sex matched controls were included in this study. All cases were subjected to thorough clinical evaluation according to a standard clinical sheet with a special stress on the state of nutrition (overt clinical signs of malnutrition, weight, height and weight for height), presence or absence of dehydration and evidence of hypovitaminosis. They were also subjected to several laboratory investigations including; complete blood count (CBC), stool analysis, culture and sensitivity and detection of rota virus, Clini-test, serum electrolytes when needed. Duodenal aspirate and jejunal biopsy when possible. Endoscopic examination of stomach and upper small intestine together with gastric mucosal biopsy for detection of Helicobacter pylori by polymerase chain reaction (PCR) were done for the patients and the control group. Results: A statistically significant difference was found between patients with persistent diarrhea and the control group regarding the incidence of H. pylori infection diagnosed by PCR technique (p < 0.05). H. pylori infection occur more commonly in infants (67%, 6/9). There was a statistically significant relationship between the prevalence of H. pylori infection and weight/height centile among patients (p < 0.05). A significant decrease in Hb level together with a very highly significant decrease in MCV values also occur in patients with positive PCR test for H. pylori infection. Moreover, there was a significant decrease in platelet count in patients with positive PCR test for H. pylori infection. Conclusion: There may be a causal relationship between H. pylori infection and persistent diarrhea. Moreover, H. pylori infection may be responsible for iron-deficiency anemia of unknown origin that is refractory to iron therapy.