Introduction: Studies have demonstrated that co-payments on medication reduce the consumption of both non-essential and essential drugs, and that the latter can lead to worse health outcomes. Far less is known about how patients cope with the cost of medication, particularly if affordability is an issue, and how this compares across two countries with different prescription charge policies. Therefore, the aim of this article is to explore empirically how, and to what extent, costs incurred by patients influence their decision-making behaviour in accessing medicines. Methods: Based on the findings from focus groups, a questionnaire was designed that addressed medication cost issues relevant to patients in both the UK and Italy. Using an econometric model, several hypotheses are tested regarding patients' decision-making behaviour and how it is influenced by health status, sociodemographic characteristics and the novel concept of a self-rated affordability measure. Results: Quite a large percentage of patients (70.3% in the UK and 66.5% in Italy) stated they have to think about the cost of medicines at least sometimes. Respondents adopted numerous cost-reducing strategies, subdivided into (i) those initiated by patients and (ii) those involving self-medication. Their use was strongly influenced by income and drug affordability problems, but the self-rated affordability measure was a stronger predictor. Commonly used strategies were not to get prescribed drugs dispensed at all, prioritising by not getting all prescribed items dispensed or delaying until the respondent got paid. Furthermore, respondents with affordability issues were also cost-conscious when self-medicating with over-the-counter (OTC) products for minor conditions such as dyspepsia. Despite patients in both countries using cost-reducing strategies, their use was more pronounced in the UK, where the prescription charge was significantly higher than in Italy. Discussion/conclusion: The results from this study provide detail on the kinds of strategies patients use to reduce the cost burden of prescription charges, and support previous research showing they may be foregoing essential medication. Because the same questionnaire was applied in two European countries, where the national health systems aim to provide healthcare services that are accessible to all citizens in need, it offers interesting insights for policy makers in other countries, where patients may have to pay a larger share of their drugs out-of-pocket, such as the US. © 2005 Adis Data Information BV. All rights reserved.