Objective To evaluate the impact of national multifaceted initiatives to improve use of proton pump inhibitors (PPIs) on the use of PPIs among older Australians. Design Interrupted time series analysis using administrative health claims data from the Australian Government Department of Veterans' Affairs (DVA). Setting Australia. Participants All veterans and dependents who received PPIs between January 2003 and December 2013. Intervention(s) National, multifaceted interventions to improve PPI use were conducted by the Australian Government Department of Veterans' Affairs Veterans' MATES programme and Australia's NPS MedicineWise in April 2004, June 2006, May 2009 and August 2012. Main outcome measure(s) Trends in monthly rate of use of any PPI among the veteran population, and the monthly rate of use of low strength PPIs among all veterans dispensed a PPI. Results Interventions in 2004, 2006, 2009 and 2012 slowed the rate of increase in PPI use significantly, with the 2012 intervention resulting in a sustained 0.04% decrease in PPI use each month. The combined effect of all four interventions was a 20.9% (95% CI 7.8-33.9%) relative decrease in PPI use 12 months after the final intervention. The four interventions also resulted in a 42.2% (95% CI 19.9-64.5%) relative increase in low strength PPI use 12 months after the final intervention. Conclusions National multifaceted programmes targeting clinicians and consumers were effective in reducing overall PPI use and increasing use of low strength PPIs. Interventions to improve PPI use should incorporate regular repetition of key messages to sustain practice change.