OBJECTIVES: Pharmaceutical expenditure is a considerable and growing cost to health care systems in Western countries.  Consequently, it is important to identify the factors influencing this rise in expenditure so as to ensure the sustainability of health systems.  The General Medical Services (GMS) scheme is a state funded scheme where eligible persons are entitled to free drugs and appliances.  The scheme covers approximately 40% of the population and GMS prescribing expenditure increased by 414% between 1998 and 2012. This research seeks to explore the rationale for this growth by investigating the composition and drivers of GMS drug expenditure in Ireland in 2012.   METHODS: A cross-sectional study was carried out on the Health Service Executive-Primary Care Reimbursement Service (HSE-PCRS) population prescribing database (n = 1,630,775). Three OLS regression models were applied to test the association between annual expenditure per claimant whilst controlling for age, sex, region, and the pharmacology of the drugs as represented by the main Anatomical Therapeutic Chemical (ATC) groups.  RESULTS: The mean annual cost per claimant was €751 (median = €211, SD = €1,323.10).  Age, sex, and regions were all significant contributory factors of expenditure, with sex having the greatest impact (β = 0.107). Those aged over 75 (β =1.195) were the greatest contributors to annual GMS prescribing costs.   When the ATC groups were included the impact of sex is diluted by the pharmacology of the products, with cardiovascular prescribing (ATC 'C') most influential (β = 1.229) and the explanatory power of the model increased from 40% to 60%.  CONCLUSIONS: This research identified significant factors (age, sex, region and  pharmacology of the drugs) influencing GMS expenditure per claimant in Ireland.  Whilst policies aimed at cost containment (co-payment charges and adjustments to GMS eligibility) can be used to curtail expenditure, health promotional programs and educational interventions should be given equal emphasis.