Deep tissue injury (DTI) is a localized area of tissue necrosis that originates in the subcutaneous layers under an intact skin and tends to develop when soft tissue is compressed for a prolonged period of time. In clinical practice, DTI is particularly common in bedridden patients and remains a serious issue in todays health care. Repositioning is generally considered to be an effective preventive measure of pressure ulcers. However, limited experimental research and no computational studies have been undertaken on this method. In this study, a methodology was developed to evaluate the influence of different repositioning intervals on the location, size and severity of DTI in bedridden patients. The spatiotemporal evolution of compressive stresses and skeletal muscle viability during the first 48 h of DTI onset was simulated for repositioning schemes in which a patient is turned every 2, 3, 4 or 6 h. The model was able to reproduce important experimental findings, including the morphology and location of DTI in human patients as well as the discrepancy between the internal tissue loads and the contact pressure at the interface with the environment. In addition, the model indicated that the severity and size of DTI were reduced by shortening the repositioning intervals. In conclusion, the computational framework presented in this study provides a promising modelling approach that can help to objectively select the appropriate repositioning scheme that is effective and efficient in the prevention of DTI.