Background: Hospital-acquired pressure injuries are a serious patient safety issue with the sacrum the most common location. Silicone foam border dressings are increasingly used in hospitalised patients, yet their clinical and cost-effectiveness in preventing pressure injuries is unclear in some patient cohorts. Objective: To determine the clinical and cost-effectiveness of a silicone foam border dressing in preventing sacral hospital acquired pressure injuries in at-risk medical-surgical patients. Methods: A prospective, multi-site, parallel group, pragmatic, superiority randomised controlled trial was conducted in Southeast Queensland, Australia. Medical-surgical adult patients (≥ 18 years) at-risk of pressure injury were recruited and randomly allocated to either an intervention (sacral dressing plus routine care) or control (routine care only) group. The Primary outcome was development of a new sacral pressure injury. Daily, blinded, and independent outcome assessments were conducted off-site for up to 14 days using edited photographs of deidentified participants' sacra. Intention-To-Treat analyses were performed using both best-case and worse-case scenarios. Additional complete case analyses were conducted as part of sensitivity analyses. Secondary outcomes comprised time to onset of hospital-acquired sacral pressure injury, severity, incidence rates per 1000 trial days (days patients were in the trial), incidence rates per 1000 hospital days (days patients were in hospital), and cost-effectiveness that compared the difference in pressure injury incidence between groups. Results: Of the 1121 eligible patients approached, 958 agreed to participate. There were no significant differences in baseline characteristics between intervention and control groups. Cumulative incidence of sacral pressure injury was 1.67 % (8/478) and 1.25 % (6/480) in the intervention and control groups respectively (p = 0.592). There was an increased risk of pressure injury for those in the intervention group (Relative Risk: 1.34 (95 % CI 0.47–3.83)), but the effect was not statistically significant and confidence intervals wide. Distribution of secondary outcomes was also similar in both the intervention and control groups. The intervention was more costly than the control showing an incremental cost of $99.90 (95 % CI $74.10–$125.60) associated with using the dressings. Conclusions: The study did not provide evidence that silicone foam border dressings reduced the incidence of sacral hospital acquired pressure injuries in adult medical-surgical patients at risk of pressure injuries. Additionally, the silicone foam dressings incurred higher incremental costs than routine care. Trial registration number: ACTRESN12619000763145, Registered 22/05/2019, first recruitment 10/07/2020.