Optimization of drug prescribing in older populations is a priority due to the significant clinical and economic costs of drug-related illness. This study aimed to: (i) estimate the prevalence of potentially inappropriate prescribing (PIP) in a national Irish older population using European specific explicit prescribing criteria; (ii) investigate the association between PIP, number of drug classes, gender and age and; (iii) establish the total cost of PIP. This was a retrospective national population study (n= 338 801) using the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. The HSE-PCRS uses the WHO Anatomical Therapeutic Chemical (ATC) classification system and details of every drug dispensed and claimants' demographic data are available. Thirty PIP indicators (STOPP) were applied to prescription claims for those >or=70 years in Ireland in 2007. STOPP is a physiological system based screening tool of older persons' potentially inappropriate prescriptions assessing drug-drug and drug-disease interactions, dose and duration. In our study population PIP prevalence was 36% (121 454 claimants). The main contributors to this were: 56 560 (17%) prescribed proton pump inhibitors at maximum therapeutic dose for >8 weeks, 29 691 (9%) prescribed non-steroidal anti-inflammatories for >3 months, 17 676 (5%) prescribed long-acting benzodiazepines for >1 month and 16 201 (5%) prescribed duplicate drugs. The main determinant of PIP was polypharmacy. The likelihood of PIP increased with a significant linear and quadratic trend (P < 0.0001) with the number of drug classes.The maximum net ingredient cost of PIP was estimated to be euro38 664 640. Total PIP expenditure was estimated to be euro45 631 319, 9% of the overall expenditure on pharmaceuticals in those >or=70 years in 2007. The findings identify a high prevalence of PIP in Ireland with significant cost consequences.