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AIM: To assess the efficacy of premedicaton with pronase or N-acetylcysteine (NAC) at 20 min before upper gastrointestinal (UGI) endoscopy and to determine whether pronase or NAC pretreatment influences the reliability of the rapid urease test.METHODS: A total of 146 patients were prospectively and randomly assigned into the study groups according to different premedications before endoscopy. One endoscopist assessed mucosal visibility (MV) with scores ranged from 1 to 4 at four sites in the stomach. The sum of the MV scores from these four locations was defined as the total mucosal visibility (TMV) score. Identification of H pylori was performed using CLO test, histology, and serology.RESULTS: The Group with pronase premedication had a significantly lower TMV score than did the groups with gascon and gascon water (P＜0.001 and P＜0.01,respectively). The group with NAC had a significantly lower TMV score than the group with gascon (P＜0.01) and a trend of a lower NV score than the group with gascon water (P = 0.06). The TMV score did not significantly differ between the group with pronase and the group with NAC (P = 0.39 and P = 0.14,respectively). The sensitivity and specificity of the CLO test were 92.5% and 93.9%, respectively, in groups premedicated with pronase and NAC together.CONCLUSION: Premedication with pronase or NAC at 20 min before UGI endoscopy improves the mucosal visibility of the stomach. Neither pronase nor NAC produces any obvious interference with the CLO test for the identification of H pylori infection.