BACKGROUND Because oropharyngeal bacteria can be brought through the abdominal wall during percutaneous endoscopic gastrostomy (PEG), peristomal infection is one of the most frequent complications in patients who undergo the procedure. This study aimed to determine whether covering the PEG tube with a sheath that could be detached in the stomach could help prevent peristomal infection. METHODS In three community hospitals in Japan, data from 449 patients with swallowing dysfunction were prospectively collected between March 2000 and February 2002 for non-covered PEG (n=206) and between March 2002 and February 2004 for covered PEG (n=243). RESULTS After adjusting for hospital, age, gender, and underlying diseases, covering the PEG significantly reduced peristomal purulent infection compared with non-covered PEG (odds ratio: 0.05; 95% confidence interval: 0.02-0.13). Body temperature, white blood cell count, and C-reactive protein at day 3 after PEG placement, as well as duration of antibiotics usage, were significantly lower or shorter in patients treated with covered PEG than non-covered PEG. In spite of the same frequencies in the two groups of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa in oropharyngeal cultures before PEG placement, these organisms were detected significantly less frequently in peristomal lesions of patients who underwent covered PEG. Moreover, 28 patients treated with covered PEG received no antibiotic therapy, and 27 of them had no signs of peristomal infection. CONCLUSIONS These results suggest that covering the PEG tube, with or without providing antibiotic therapy, may prevent peristomal infection in spite of the presence of oropharyngeal bacterial flora after percutaneous endoscopic gastrostomy.