OBJECTIVES:To investigate whether pantoprazole (20 mg/d) produces significantly greater symptom control than ranitidine (300 mg/d) in patients with gastro-oesophageal reflux disease (GORD). DESIGN:Multicentre, randomised, double-blind, parallel-group comparison. SETTING:76 general practices in north-west Sydney and Newcastle, New South Wales (Australia), from 19 January 1999 to 22 September 2000. PATIENTS:307 patients aged 18 years or over presenting with symptomatic GORD. INTERVENTIONS:Pantoprazole (20 mg once daily) or ranitidine (150 mg twice daily). MAIN OUTCOME MEASURES:Patient-assessed frequency and severity of heartburn using the Gastrointestinal Symptom Rating Scale (GSRS) and a patient heartburn diary. RESULTS:Pantoprazole was associated with significantly higher rates of complete control of GORD symptoms than ranitidine at four weeks (40% v 19%; P < 0.001), eight weeks (55% v 33%; P < 0.001), six months (71% v 56%; P = 0.007) and 12 months (77% v 59%; P = 0.001). CONCLUSIONS:Low-dose pantoprazole is an effective alternative to standard-dose ranitidine for initial and maintenance treatment of patients with symptomatic GORD.