OBJECTIVES: To examine the new co-payment scheme for prescribed medications introduced in Spain in 2012 and to explore differences in patient and National Health Service (NHS) drug cost co-payments between the old and the new schemes, using an example in a modelled patient population with coronary heart disease (CHD). METHODS: The new legislation was researched and the new co-payment scheme was summarised in a flowchart. A published economic evaluation of drug-eluting versus bare metal stents for high-risk patients with CHD was used to calculate co-payments for the total cost of a prescribed drug (clopidogrel) from patients and from the NHS. The patient contribution was estimated from the income and expected work status of the model’s population. RESULTS: In the new co-payment scheme, pharmacy-dispensed drugs are divided into three categories, using the Anatomical, Therapeutic, and Chemical classification system: 1) reimbursed with reduced contribution (4.26 € per prescription in 2014), 2) reimbursed without reduced contribution (ranging from 40% to 60%, depending on declared incomes for active workers, and from 10% to 60% for retired people) and 3) not reimbursed. Monthly limits for retired people (in 2014) range from 8.26 € to 62 €, with a monthly limit of 0.426 € for long-term, chronic conditions. The current, monthly, over-the-counter price of clopidogrel is 22.92 €. Under the old co-payment scheme, the model estimated that the average NHS payment was 19.62 € per patient (86% of the cost). Under the new scheme, this amount was estimated at 16.55 € (72%). The NHS contribution decreased by 14%. CONCLUSIONS: The new scheme results in a significant reduction to drug-related NHS co-payment contributions. This reduction could lead to significant changes in incremental cost-effectiveness ratio estimates. It is recommended that this adjustment be made in economic evaluations developed or adapted for Spain.