Proton pump inhibitors (PPIs) are one of the most commonly prescribed drugs in the United States owing to their clinical efficacy and relative lack of adverse effects. PPIs have largely replaced H2 receptor antagonists in the treatment of gastro intestinal disorders related to acid hypersecretion. Inspite of a number of local and international guidelines, the use of PPIs has increased rapidly and the expenditure on these agents has increased dramatically. The main aim of this study was to describe the prescribing patterns of omeprazole in outpatient clinics at Sultan Qaboos University Hospital (SQUH) and compare it with local and international guidelines as well as to assess the cost impact of its prescribing. A retrospective observational study was performed over a 6-month period from the 1st of July to 31st of December in 2009, in outpatients who attended gastroenterology and non gastroenterology clinics at SQUH. Omeprazole was the prototype PPI selected for the study because it is the most commonly prescribed PPI in SQUH. A customized data collection form was used to record information which was entered in a computerized database. The total number of prescriptions dispensed during the study period was 2,622. However, after excluding children and adults under 18 years of age, and patients with a history of upper gastrointestinal bleeding, the sample size was reduced to 1,662. From this pool, a random sample selection of 30% was undertaken to obtain a sample size of 499 which represented the study cohort. The cost was derived by multiplying the unit cost of each capsule of omeprazole to the total number of capsules prescribed during the study period. Descriptive statistics were used to illustrate the prescribing pattern of omeprazole. Multivariate logistic regression model were used to study the association between omeprazole prescriptions and other study variables. Thirty one percent of the prescriptions were from the gastroenterology outpatient clinic while 69% were from other clinics. Omeprazole was prescribed for different indications. In 27% of the patients it was prescribed for those who were prescribed drugs associated with ulcers. Ten percent of the patients had prescriptions for gastritis, 25% for dyspepsia, 4% for peptic ulcer disease, 16% for gastroesophageal reflux disease (GERD), 6% for the eradication of Helicobacter pylori and 12% there was no documentation. Eighteen percent of the cohort had overprescribing (20% of females and 14% of males). The multivariate logistic regression model showed that males were 38% less likely to have overprescribing compared to females. Furthermore, gastroenterology clinics were 96% more likely to have overprescribing than non gastroenterology clinics. With respect to age, the model indicated that, generally, the odds of having overprescribing increased with age. However, this did not attain statistical significance. With regards to cost, it was found that the total number of extrapolated omeprazole 20 mg capsules utilized during the six months period for the study cohort was 30,812 capsules with a total cost of 863 R.O. (30,812 * 0.028). Overprescriptions accounted for approximately 3620 extra capsules of omeprazole in 6 months with an additional cost of 101 R.O. (3620 * 0.028) Generally, omeprazole prescribing at SQUH was appropriate in terms of indications but inappropriate in terms of length of therapy. Rational drug prescribing is needed to avoid unnecessary drug cost in order to maximize benefit from the available limited resources.