Aim: To systemically synthesise the evidence on the most effective nursing interventions to prevent pressure injuries among critical care patients. Background: Although pressure injury (PI) prevention is a focus of nursing care in critical care units, hospital-acquired pressure injuries continue to occur in these settings. Design: A systematic review of literature guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Synthesis without meta-analysis (SWiM) guidelines. Methods: Four electronic databases were searched for relevant studies. Included studies were screened and then critically appraised using the appropriate Joanna Briggs Institute appraisal tool. Data were analysed and reported using a narrative synthesis. Results: The review included 14 studies. Randomised controlled trials, quasi-experimental, case series and cross-sectional studies were included. The review identified four broad categories of interventions that are the most effective for preventing pressure injuries: (a) PI prevention bundles, (b) repositioning and the use of surface support, (c) prevention of medical device-related pressure injuries and (d) access to expertise. All the included studies reported a reduction in pressure injuries following the interventions; however, the strength of the evidence was rated from moderate to very low. Conclusions: Nurses are well qualified to lead in the prevention of pressure injuries in critical care units. Every critically ill patient requires interventions to prevent pressure injuries, and the prevention of PIs should be considered a complex intervention. Nurses must plan and implement evidence-based care to prevent all types of pressure injuries, including medical device-related pressure injuries. Education and training programmes for nurses on PI prevention are important for prevention of pressure injuries. Relevance to clinical practice: Nursing interventions should consist of evidence-based ‘bundles’ and be adapted to patients’ needs. To prevent pressure injuries among critically ill patients, nurses must be competent and highly educated and ensure fundamental strategies are routinely implemented to improve mobility and offload pressure.