Background and Objectives: Helicobacter pylori (H. pylori) infection impairs quality of life. However, whether eradication therapy ameliorates gastrointestinal symptoms remains questionable. The main objective of this study was to evaluate the influence of H. pylori eradication therapy on gastrointestinal symptoms. Materials and Methods: A total of 140 patients, 59 women and 81 men, with a mean age of 61 and suffering from H. pylori infection in the University Hospital of Split, Croatia, were enrolled in the study. Patients were randomly assigned to either concomitant or hybrid therapies. The Gastrointestinal Symptom Rating Scale (GSRS) questionnaire was completed by patients prior to and after the eradication therapy. Results: In both groups, the total GSRS score improved significantly after therapy. In the concomitant group, the abdominal pain score, reflux symptoms score and indigestion score decreased significantly after therapy. In the group with hybrid therapy, all five groups of symptoms (abdominal pain, reflux symptoms, indigestion, diarrhea and constipation) significantly decreased after therapy. Patients with adverse events had significantly higher total GSRS scores after eradication therapy. Conclusions: H. pylori eradication therapy could alleviate gastrointestinal symptoms regardless of the treatment used, but the favorable effect seemed to be more pronounced after hybrid therapy.