Aims: To compare safety and efficacy of on- demand pantoprazole 20 mg/40 mg versus placebo in the long- term management of patients with mild gastroesophageal reflux disease (GERD) after heartburn relief. Methods: A total of 634 patients with endoscopically confirmed GERD grade 0/I and heartburn were included. During the acute phase, patients were treated with pantoprazole 20 mg once daily for 4 weeks. Those patients relieved from heartburn entered the long- term phase, and were randomly assigned to either treatment group pantoprazole 20 mg, 40 mg or placebo. Over 6 months, patients took study medication on demand (antacids as rescue medication) and discontinued the drug once symptoms abated. Results: After 4 weeks a total of 87.1% /90.0% of patients were free of heartburn (ITT/PP), and entered the subsequent long- term phase. The perceived average daily symptom load (placebo: 3.93, pantoprazole 20 mg: 2.91, pantoprazole 40 mg: 2.71, ITT) and the number of antacid tablets taken (average number, placebo: 0.68, pantoprazole 20 mg: 0.45, pantoprazole 40 mg: 0.33, ITT) were significantly higher in the placebo than in both pantoprazole groups (p < 0.0001), with no statistically significant difference between the two pantoprazole groups. The discontinuation rate due to insufficient control of heartburn was significantly lower in both pantoprazole groups compared to placebo (placebo: 10.9, pantoprazole 20 mg: 2.8, pantoprazole 40 mg: 0.9, ITT). Conclusions: Our findings favor on- demand treatment with pantoprazole 20 mg for the long- term management of heartburn in patients with uncomplicated GERD (grade 0/I) with superiority to placebo. Aims: To compare safety and efficacy of on-demand pantoprazole 20 mg / 40 mg versus placebo in the long-term management of patients with mild gastroesophageal reflux disease (GERD) after heartburn relief. Methods: A total of 634 patients with endoscopically confirmed GERD During the acute phase, the patients were treated with pantoprazole 20 mg once daily for 4 weeks. Those patients relieved from heartburn entered the long-term phase, and were randomly assigned to either treatment group pantoprazole 20 mg , 40 mg or placebo. Over 6 months, patients took medication on demand (antacids as rescue medication) and discontinued the drug once symptoms abated. Results: After 4 weeks a total of 87.1% /90.0% of patients were free of heartburn ( ITT / PP), and entered the subsequent long-term phase. The perceived average daily symptom load (placebo: 3.93, pantoprazole 20 mg: 2.91, pantoprazole 40 mg: 2.71, ITT) and the number of antacid tablets taken e number, placebo: 0.68, pantoprazole 20 mg: 0.45, pantoprazole 40 mg: 0.33, ITT) were significantly higher in the placebo than in both pantoprazole groups (p <0.0001) with no statistically significant difference between the two pantoprazole groups. discontinuation rate due to insufficient control of heartburn was significantly lower in both pantoprazole groups compared to placebo (placebo: 10.9, pantoprazole 20 mg: 2.8, pantoprazole 40 mg: 0.9, ITT). Conclusions: Our findings favor demand-treatment with pantoprazole 20 mg for the long-term management of heartburn in patients with uncomplicated GERD (grade 0 / I) with superiority to placebo.