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Aim: To evaluate the microscopic histopathological changes in duodenal tissue and its relationship to the severity of symptoms in patients with functional dyspepsia while taking the effect of Helicobacter pylori (H. pylori) infection into account., Methods: Several gastric and duodenal biopsy specimens were obtained in 217 patients with functional dyspepsia and were evaluated for H. pylori infection and histopathological changes. Severity of symptoms was assessed by Leeds Dyspepsia Questionnaire (LDQ) and its relationship to histopathological changes and H. pylori infection status was assessed., Results: Helicobacter pylori infection was associated with presence and severity of microscopic duodenitis (p < 0.001). In H. pylori-infected patients, the presence of microscopic duodenitis was independent of microscopic gastritis (p = 0.74). Severity of dyspepsia symptoms was not higher in H. pylori-infected patients than non-infected patients (p = 0.15), but in the presence of H. pylori infection and microscopic gastritis, microscopic duodenitis significantly worsened the LDQ symptom severity score (p < 0.001). In multivariate analysis, the odds of experiencing severe symptoms in patients with severe microscopic duodenitis was 2.22 times greater than in individuals with very mild, mild, or moderate duodenitis., Conclusions: Microscopic duodenitis in H. pylori-infected patients may play a major role in producing and aggravating symptoms in FD patients and may be a determinant factor to consider in whether to treat H. pylori infection in functional dyspepsia.