Despite the implementation of prevention strategies, pressure ulcers (PUs) continue to be a challenging health problem for patients (and their carers), clinicians and health-care providers. One area of growing interest is the use of prophylactic dressings (which were originally designed for the treatment of PUs and other wound types) as a component of standard prevention measures. Over the past few years, a large amount of scientific and clinical data relating to this subject has been published in peer-reviewed journals and presented at international meetings and conferences. A substantial proportion of these data relate to one group of dressings: multi-layer foam dressings with Safetac, which are manufactured by Mölnlycke Health Care (Gothenburg, Sweden). This evidence pool has influenced the experts involved in updating the Clinical Practice Guideline, produced by the National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel and Pan Pacific Pressure Injury Alliance, on the prevention and treatment of PUs. The updated Guideline, published in 2014, recommends that, as part of their PU prevention regimens, clinicians should consider applying prophylactic dressings to bony prominences in anatomical areas that are frequently subjected to friction and shear. A literature review was undertaken to identify clinical data from the entire evidence hierarchy, as well as scientific data from laboratory studies, on the use of multi-layer foam dressings with Safetac in the prevention of pressure ulceration. The MEDLINE (National Library of Medicine, Bethesda, US) and EMBASE (Elsevier B, Amsterdam, Netherlands) bibliographic databases were searched. In addition, abstract books and proceedings documents relating to national and international conferences were scanned in order to identify presentations (i.e. oral, e-posters and posters) of relevance to the review. Clinical and health economic experts have undertaken numerous studies, including randomised controlled trials, to assess the efficacy and cost-effectiveness of using multi-layer foam dressings with Safetac as a component of standard PU prevention strategies. The results of these studies indicate that the application of multi-layer foam dressings containing Safetac can reduce the occurrence of PUs on anatomical locations such as the sacrum and the heel, and underneath medical devices. Scientists have also developed and used laboratory methods to gain a better understanding of how prophylactic dressings work. The results of these studies indicate that the composition of foam dressings containing Safetac (i.e. their multi-layer structure) sets them apart from other dressings due to their ability to mediate the effects of physical forces (i.e. pressure, friction and shear) and control microclimate, all of which contribute to pressure ulceration. The evidence pool clearly indicates that the prophylactic use of multi-layer foam dressings with Safetac as a component of standard prevention measures is beneficial to the clinician, the health-care provider and the patient. It should be noted that the findings outlined in this review may not be transferable to other products as their makeup and components are likely to differ significantly from those of multi-layer foam dressings with Safetac. As the importance of evidence-based practice and the need for cost-effective care continues to grow, clinicians and provider should carefully consider this point when selecting prophylactic dressings for PU prevention.