Co-payments have been linked to the slowing growth in pharmaceutical spending over the last five years. However, patients with health problems frequently have difficulty affording their pharmacotherapy and fail to take their medication as prescribed. We examine the relationship between co-payment amounts and four types of cost-related underuse: taking fewer doses, postponing taking a medication, failing to fill a prescription at all, and taking medication less frequently than prescribed. We conducted a nationwide survey of US adults age 50 and over who take medication for a chronic condition. Participants provided information on 17 chronic conditions, medication they take for those conditions, and whether they underused any medication due to cost. We analyzed those who reported paying co-payments for their prescriptions (n = 2,869). Analysis involved multivariate logistic regression, with adjustments for survey weights and clustering. Our data show a strong positive association between co-payments and cost-related medication underuse. Although people differ in how they underuse medications, these behaviours are strongly associated with co-payment amount. Realigning the co-payments with cost-effectiveness data, also known as value-based insurance design, warrants further investigation.