Objectives The study determined a comparative three-year trend in prescribing volumes and costs of proton pump inhibitors in three outpatient specialties of a tertiary hospital. Methods Prescription data for three consecutive fiscal years (2016–2018) were extracted from a tertiary hospital electronic database, for the gastrointestinal, cardiovascular and orthopaedic outpatient specialties. The data collected were individual proton pump inhibitors, overall and individual prescribing volumes (capsule/tablet) and costs, stratified by specialty and fiscal year. Key findings Of the three specialties, the largest volume of proton pump inhibitor prescriptions, mostly for omeprazole, comes from the orthopaedic specialty (46%). In terms of prescribing costs, at the top is the cardiovascular specialty (45.75%). Lansoprazole, which is one of the proton pump inhibitors on in the national list of essential medicines, contributed most to the cost. Prescribing proton pump inhibitors that are not included in the national list of essential medicines were responsible for over 90% of the costs in the cardiovascular and gastrointestinal specialties. An escalating trend in prescribing varied proton pump inhibitors, that is, esomeprazole, lansoprazole, pantoprazole, dexlansoprazole and rabeprazole, all of which were not on the list of essential medicines, was evident in the latter. Conclusions The highest volume of proton pump inhibitor prescribing—mostly of omeprazole, was issued by the orthopaedic specialty. The cardiovascular specialty was responsible for the largest amount of cost. The increases in the uses and costs of varying proton pump inhibitors which were outside the national list of essential medicines were notable in the gastrointestinal specialty.