Transactions involving medicines are typically asymmetric: although neither buyer nor seller has complete information about a product’s quality and efficacy – particularly in settings like Ghana with weak regulation – the uncertainty and risks are most pressing for the buyer. Drawing on in-depth interviews (N=220) and observations of medicine transactions, plus interviews with regulators (N=20), we explore how people in Ghana negotiate this uncertainty. In contrast with prevailing literature that emphasises the role of trust in managing healthcare, our data suggest that distrust may be an equally important departure point. Starting from a position of underlying distrust, most of our interviewees took precautions, scrutinising the medicine, and the outlet and retailer, before making a purchase. Where buyers acted on trust (taking no precautions), this was underpinned either by necessity or by deeply embedded social relationships between seller and buyer that render precaution-taking both unnecessary and counter-productive. However, trust embedded in social relationships cannot eliminate risk, because of the dispersed and under-regulated nature of wider supply chains.