Aim: To compare the efficacy of prokinetic agents and proton pump inhibitors in symptom relief of patients with non-ulcer dyspepsia. Design: Comparative prospective single blind clinical trial. Patients and setting: Fifty four cases of non-ulcer dyspepsia in whom H. pylori has been eradicated were seen in the specialist gastroenterology clinic of a tertiary care hospital. Methodology: Patients with dyspepsia and negative endoscopy for peptic ulcer disease, gastro-oesophageal reflux disease, hiatus hernia and upper gastrointestinal malignancy in whom H pylori has been eradicated but still had dyspepsia were assessed and scored using the modified Glasgow dyspepsia severity score (GDSS) at baseline. They were then randomized to receive domperidone or oesomeprazole for three months and the GDSS evaluated monthly over a three month period. Results: Twenty eight patients were randomized to receive domperidone and 27 patients received oesomeprazole. All the patients were evaluated in the first month, 96% in the second month and 87% in third month. The mean GDSS at baseline was 4.68±1.49 for domperidone and 5.0±2.06 for oesomeprazole p=0.59. The rank of the scores at baseline was 5 for domperidone and 5 for oesomeprazole. There were no significant differences between the scores for domperidone and oesomeprazole using Mann Whitney analysis. The percentage of patients who scored less than 1 on the modified GDSS at one month was 29.2% for domperidone and 33% for oesomeprazole, p=0.741; at two months 43.5% for domperidone and 30.8% for oesomeprazole, p=0.357; and at three months 54.5% for domperidone and 40.9% for oesomeprazole, p=0.365. The odds of improving while on domperidone as compared to oesomeprazole was 0.824, 95% CI 0.251-2.700 in the first month, 1.731, 95% CI 0.536-5.587 in the second month and 1.733 95% CI 0.525-5.723 in the third month. Conclusion: Domperidone and oesomeprazole are equiefficacious in relieving dyspepsia symptoms amongst H. pylori negative non-ulcer dyspepsia patients when given continuously for three months.