Poor compliance of prescription medication is an ongoing public health crisis. Nearly half of patients do not take their medication as prescribed, harming their own health while also increasing public health care costs. Despite these detrimental consequences, prior research has struggled to establish cost-effective and scalable interventions to improve adherence rates. We suggest that one reason for the limited success of prior interventions is that they make the personal health costs of non-adherence insufficiently prominent, while a higher saliency of these costs may motivate patients to adhere more. In the current research, we test whether an intervention that makes the personal health costs of non-compliance more salient for patients will increase their medication adherence. To do so, we conducted a randomized controlled trial with 16,191 patients across 278 UK pharmacies over a 9-month time period and manipulated the perceived consequences of medication non-adherence. We find that patients who received a treatment highlighting the personal health costs of non-compliance were significantly more likely to adhere to their medication than three comparison groups (odds ratio = 1.84, 95% confidence interval = 1.37–2.47). Shifting patients’ focus to the personal health costs of non-compliance may thus offer a potentially cost-effective and scalable approach to improving medication adherence.