AIM: To compare efficacy and tolerability of four proton pump inhibitors (PPIs) commonly used in the short-term therapy of esophagitis in elderly patients.METHODS: A total of 320 patients over 65 years with endoscopically diagnosed esophagitis were randomly assigned to one of the following treatments for 8 wk:(1) omeprazole 20 mg/d; (2) lansoprazole 30 mg/d;(3) pantoprazole 40 mg/d, or (4) rabeprazole 20 mg/d.Major symptoms, compliance, and adverse events were recorded. After 8 wk, endoscopy and clinical evaluation were repeated.RESULTS: Per protocol and intention to treat healing rates of esophagitis were: omeprazole = 81.0% and 75.0%, lansoprazole = 90.7% (P = 0.143 vs omeprazole) and 85.0%, pantoprazole=93.5% (P = 0.04vs omeprazole) and 90.0% (P = 0.02 vs omeprazole),rabeprazole = 94.6% (P = 0.02 vs omeprazole) and 88.8% (P = 0.04 vs omeprazole). Dividing patients according to the grades of esophagitis, omeprazole was significantly less effective than the three other PPIs in healing grade 1 esophagitis (healing rates:81.8% vs 100%, 100% and 100%, respectively, P =0.012). Pantoprazole and rabeprazole (100%) were more effective vs omeprazole (89.6%, P = 0.0001)and lansoprazole (82.4%, P = 0.0001) in decreasing heartburn. Pantoprazole and rabeprazole (92.2% and 90.1%, respectively) were also more effective vs lansoprazole (75.0%, P ＜ 0.05) in decreasing acid regurgitation. Finally, pantoprazole and rabeprazole (95.2% and 100%) were also more effective vs lansoprazole (82.6%, P ＜ 0.05) in decreasing epigastric pain.CONCLUSION: In elderly patients, pantoprazole and rabeprazole were significantly more effective than omeprazole in healing esophagitis and than omeprazole or lansoprazole in improving symptoms.H pylori infection did not influence the healing rates of esophagitis after a short-term treatment with PPI.