OBJECTIVES: To evaluate the cost-effectiveness of esomeprazole (40 mg once daily [od]) in adolescent patients with moderate or severe reflux oesophagitis (RO), Los Angeles grades C or D compared with standard adult doses of other proton pump inhibitors (PPIs), i.e., generic lansoprazole 30 mg od, generic omeprazole 20 mg od, pantoprazole 40 mg od, and rabeprazole 20 mg od. METHODS: A simple decision-tree model was designed to evaluate the cost-effectiveness of esomeprazole over a 6-month time horizon from the perspective of the UK National Health Service. Healing rate probabilities were extrapolated from the results of a meta-analysis of 6 randomised, controlled trials that compared esomeprazole with other PPIs in adults who had endoscopically-confirmed RO. Data from the IMS Disease Analyser was used to estimate the average duration of a course of PPI therapy prescribed to adolescents in the UK. Health state valuations were estimated from a European study that used Time Trade Off to obtain utilities scores from a sample of more than 1,000 patients with GORD symptoms. RESULTS: Esomeprazole was a cost-effective treatment option for adolescents with moderate or severe RO versus all other standard-dose PPIs. For example, incremental cost-effectiveness ratios ranged from £2,200/QALY (95% CI, £1,100/QALY to £5,600/QALY) and £15,200/QALY (95% CI, £6,700 to >£80,000/QALY), when esomeprazole was compared with pantoprazole (in adolescents with severe RO) and generic lansoprazole (in adolescents with moderate RO), respectively. The probability of esomeprazole being cost-effective at a threshold of £30,000/QALY was greater than 84% for all the analyses that were undertaken. CONCLUSION: Esomeprazole is a cost-effective treatment for adolescent patients who are presumed to have moderate or severe reflux oesophagitis.