OBJECTIVES: Proton pump inhibitors (PPI) are not always added to the treatment of low dose acetylsalicylic acid (LDASA), but is proven to be effective in preventing upper gastrointestinal toxicity. However, PPI’s may also have additional side effects that could influence the cost and quality of life of patients. To assess the cost-effectiveness of adding a PPI compared to no PPI co-treatment in older patients LDASA.  METHODS: A cost-effectiveness study was conducted with a Markov model for PPI co-medication (intervention) compared to no PPI co-medication (usual care) in LDASA users. The base case analysis was performed for patients of 70 years old. The models addressed chronic LDASA use of five years. Incremental cost-utility ratio’s (ICURs), expressed as costs per QALY gained, were calculated for different age categories (60 up to 80 years) accounting for different risk rates for side effects from LDASA or PPI use. These side effects included gastrointestinal bleeding, dyspepsia, pneumonia and hip fractures. Finally, a budget impact analysis was performed to assess the health care expenditures to add PPIs in all current patients using LDASA above the age of 60 years in the Netherlands. RESULTS: Adding a PPI to LDASA, compared to not adding a PPI, resulted in incremental costs of € 71,84 and incremental effects of 0,006 QALY’s and an ICUR of € 11,491.53/QALY gained for the base case analysis. The ICUR for 60- and 80-year old patients was € 11,491.53/QALY and € 53,860.85/QALY, respectively. The total budget impact of adding a PPI to current LDASA users (≥ 60 years) was €174,475,296. CONCLUSIONS: Adding a PPI to LDASA users may be a cost-effective approach in patients from 60 up to 80 years old. However, with increasing age the costs became higher and the effects lower, due to higher risks of the different side effects.