Functional dyspepsia (FD) is very common, but the pathogenesis of Helicobacter pylori leading to FD is still debated. The aim of this study was first to evaluate the impact of H. pylori colonization on the efficacy of Paspertase (a metoclopramide plus exogenous enzymes regimen for FD patients) and, second, to compare the prevalence of H. pylori infection in FD patients with the general population. Seventy-four consecutive FD patients were enrolled undergoing Paspertase treatment. The symptomatic response was evaluated according to 1-4 scales of six main dyspeptic symptoms (i.e. epigastric pain/discomfort, early satiety, heartburn, nausea/vomiting, abdominal fullness/bloating, and belching). Nine hundred and seventy healthy subjects undergoing a paid physical check-up were included to study the status of H. pylori colonization. The demographic data and basal symptom scores between 43 H. pylori-positive and 31 H. pylori-negative patients were not significantly different. Total and individual symptom scores improved significantly after 4 weeks of Paspertase therapy (P < 0.05), irrespective of H. pylori infection. The prevalences of H. pylori were very similar in FD patients and the general population (58.1 vs 58.0%, NS). In conclusion, these observations suggest that H. pylori colonization is not significant in FD patients of Taiwan while a short-term prokinetic medication is effective for these patients, irrespective of H. pylori status.