In 249 patients with acute symptomatic reflux esophagitis grade II and III (Savary-Miller classification), we compared the efficacy and safety of pantoprazole, a newly developed proton pump inhibitor given at a once-daily dose of 40 mg, with a standard dose of the H2 receptor antagonist ranitidine (150 mg b.i.d.) in a randomized, double-blind, multicenter study. Complete healing was achieved after 4 and 8 weeks of therapy (protocol-correct) in 69 and 82% (pantoprazole) and 57 and 67% (ranitidine), respectively (p = 0.054 at 4 weeks and p < 0.01 at 8 weeks). The predominant symptoms of gastroesophageal reflux, i.e., heartburn and acid eructation, were more effectively reduced in pantoprazole- than in ranitidine-treated patients. The frequency of adverse events was low and did not differ between the two treatment groups. We conclude that pantoprazole is superior to ranitidine in the acute treatment of reflux esophagitis.