The purpose of this study was to determine the cost for prevention and treatment of pressure ulcers from a hospital perspective and to identify the least resource-intensive pressure ulcer prevention strategy. Cost analyses were examined from a hospital perspective using direct costs. The study was carried out alongside a prospective cohort study on the incidence and risk factors for pressure ulcers. Two large teaching hospitals in the Netherlands with (partly) opposing approaches in prevention, a technological versus a human approach, were analyzed. The main outcome measures were resource use, costs of preventive measures and treatment, and pressure ulcer incidence in both hospitals. Pressure ulcer prevention through a predominantly technical approach resulted in a similar incidence rate as prevention through a predominantly human approach. However, the technical approach was considerably less expensive.