Background: Pressure ulcers are serious, avoidable, costly and common adverse outcomes of healthcare. Objectives: To evaluate the cost-effectiveness of a patient-centred pressure ulcer prevention care bundle compared to standard care. Design: Cost-effectiveness and cost-benefit analyses of pressure ulcer prevention performed from the health system perspective using data collected alongside a cluster-randomised trial. Settings: Eight tertiary hospitals in Australia. Participants: Adult patients receiving either a patient-centred pressure ulcer prevention care bundle (n = 799) or standard care (n = 799). Methods: Direct costs related to the intervention and preventative strategies were collected from trial data and supplemented by micro-costing data on patient turning and skin care from a 4-week substudy (n = 317). The time horizon for the economic evaluation matched the trial duration, with the endpoint being diagnosis of a new pressure ulcer, hospital discharge/transfer or 28 days; whichever occurred first. For the cost-effectiveness analysis, the primary outcome was the incremental costs of prevention per additional hospital acquired pressure ulcer case avoided, estimated using a two-stage cluster-adjusted non-parametric bootstrap method. The costbenefit analysis estimated net monetary benefit, which considered both the costs of prevention and any difference in length of stay. All costs are reported in AU$(2015). Results: The care bundle cost AU$144.91 (95%CI: $74.96 to $246.08) more per patient than standard care. The largest contributors to cost were clinical nurse time for repositioning and skin inspection. In the cost-effectiveness analysis, the care bundle was estimated to cost an additional $3296 (95%CI: dominant to $144,525) per pressure ulcer avoided. This estimate is highly uncertain. Length of stay was unexpectedly higher in the care bundle group. In a cost-benefit analysis which considered length of stay, the net monetary benefit for the care bundle was estimated to be −$2320 (95%CI −$3900, −$1175) per patient, suggesting the care bundle was not a cost-effective use of resources. Conclusions: A pressure ulcer prevention care bundle consisting of multicomponent nurse training and patient