Pantoprazole is a new proton pump inhibitor with a potent antisecretory activity, well defined pharmacokinetics and safety profile. The aim of this single blind, randomized clinical trial was to compare the efficacy of pantoprazole (PAN) 40 mg/day and omeprazole (OME) 20 mg/day in patients with grade I and II GERD (Savary-Miller classification). A total of 120 patients were included (PAN = 60 and OME = 60). In the per protocol/analysis, healing rates at 4 weeks were 76.3% PAN and 71.2% OME (ns), and at 8 weeks 94.7% PAN and 92.9% OME (ns). In the intention to treat analysis, healing rates at 4 weeks were 75% PAN and 70% OME (ns), and at 8 weeks 90% PAN and 86.6% OME (ns). Both pantoprazole and omeprazole were well tolerated with no serious drug related adverse events. Pantoprazole 40 mg/day was found to be safe and effective therapy comparable to omeprazole 20 mg/day in the short-term treatment for reflux esophagitis (grade I and II).