BACKGROUND: Proton pump inhibitors (PPIs) remain one of the world's most frequently prescribed medications and there is a growing number of publications on correct versus incorrect use of PPIs worldwide. The objective of this observational retrospective study was to assess changes in PPI prescribing trends over the past decade and pharmacists' effect on optimizing PPI prescribing practice at a tertiary hospital in China. METHODS: We collected the prescriptions of PPIs in our hospital from January 2007 to December 2016. Then the rate of PPI prescribing, the defined daily doses (DDDs) and expenditures were calculated and plotted to show the change in utilization of and expenditure on PPIs. Reasons behind this change and effect of pharmacists' intervention were evaluated by investigating the rationality of PPI use through sample surveys of patients of pre-intervention (Jul.-Dec. 2015) and post-intervention (Jul.-Dec. 2016). RESULTS: In outpatient settings, the rate of PPI prescribing remained almost constant, utilization (from 135,808 DDDs to 722,943 DDDs) and expenditure (from 1.85 million CNY to 7.96 million CNY) increased for the past ten years, dominated by oral formulations and rabeprazole. In contrast, in inpatient settings, the rate of PPI prescribing (from 20.41 to 37.21%), utilization (from 132,329 DDDs to 827,747 DDDs) and expenditure (from 3.15 million CNY to 25.29 million CNY) increased from 2007 to 2015 and then decreased, dominated by injection formulations and omeprazole. Pharmacist interventions could significantly promote the rational use of PPIs (44.00% versus 26.67%), decrease PPI use and reduce patients' charges (P < 0.05). CONCLUSIONS: The utilization of and expenditure on PPIs grew due to the increase of patients and irrational use of PPI. Pharmacist interventions help to reduce PPI utilization and expenditure and enhance rationality for inpatients, but much work should be done to regulate injection and originator formulas, and improve the rationality in the future.