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Introduction: Helicobacter pylori (H. pylori) is suggested to play a role in dyspepsia. The aim of this study was to assess the prevalence of H. pylori, in dyspeptic patients. Methods: This cross-sectional study was conducted on 850 patients with dyspepsia in Iran (2006-2007). The patients were selected using convenience sampling method. Data was collected using ROME III criteria questionnaire. Patients who consumed antibiotics one month before the study were excluded. Urea breath test (UBT) was performed for diagnosis of H. pylori infection and patients with a UBT value above 25 were considered as positive for H. pylori infection. Results: Among 782 patients, 540 (69%) were female and 242 (31%) were male, with the average age of 35.3±18. The prevalence of H. pylori infection was 72.1% (564). There was a significant correlation between H.pylori with age and gender (p<0.05). The prevalence of H. pylori among patients without abdominal fullness, gastroesophasial reflux, peptic ulcer and gastrointestinal bleeding was significantly higher than those with positive history of dyspeptic symptoms (p 0.05). Conclusion: The prevalence of H. pylori in southern Iran is higher than other areas. Screening and treating patients with dyspeptic symptoms are recommended.