Introduction: In the primary care setting, proton pump inhibitor (PPI) overutilisation often stems from the failure to discontinue prophylaxis treatment prior to tertiary care discharge and consider step-down therapy following discharge. Long-term PPI use can result in potential drug-related problems and unnecessary drug expenditure. This study aimed to evaluate the effectiveness of pharmacist-structured review in reducing inappropriate PPI prescriptions and estimate the potential cost saving. Methods: This non-randomised controlled study was conducted for 16 weeks at 17 government health clinics in Selangor, Malaysia. Eligible patients attending the outpatient pharmacies of intervention clinics were recruited consecutively and their consent was obtained. A structured review of PPIs was performed in which pharmacists identified patient demographics, indications and the length of PPI therapy using a PPI intervention form. Recommendations were discussed with physicians before prescription changes were made and documented. Moreover, standard management was conducted in the control clinics. Results: A total of 568 patients with prescriptions containing PPIs were sampled, with a total of 284 patients being placed into the control and intervention groups, respectively. Compared to the control group, inappropriate PPI utilisation in the intervention group significantly decreased from 79.9 to 30.4% (p<0.05). The changes to PPI prescriptions observed in the intervention group included: stop PPI therapy (30.8%), step-down therapy (22.9%), start substitution therapy (15.9%) and no change (30.4%). The physicians’ acceptance rate for pharmacist intervention was 67.8%. A 66.1% reduction in monthly PPI pill count and a 72.0% reduction in monthly medication expenditure (RM44.85/patient/year) were observed. Conclusion: The pharmacist-structured review was effective in increasing appropriate PPI utilisation and led to substantial cost savings.