The incidence of pressure ulcers remains high in patients with moderate to severe acute respiratory distress syndrome, ventilated in the prone position. A digital platform, dedicated to prone positioning and skin/tissue damage education was developed. To evaluate the impact of the PRONEtect Education Hub versus a traditional lecture on final-year nursing students’ confidence levels and knowledge in a non-inferiority study. A multicenter, non-blinded, parallel-group, non-inferiority study with equal randomization (1:1 allocation) was conducted at two nursing schools in Belgium. Clinicaltrials.gov (NCT05575869). Following baseline assessments, the control group received a 1-h classroom lecture, and the experimental group gained access to the PRONEtect website. Three weeks later, participants completed the knowledge, confidence, and visual knowledge assessment. At baseline, 67 of the 80 participants completed the assessments and post-intervention, 28 and 27 participants respectively completed the confidence, knowledge, and visual knowledge assessments (dropout rate of 66.25%). Confidence levels: a mean ratio of relative change from baseline = 0.96 (Control (C)/Experimental (E)); 97.5% confidence interval (CI): 0.74 to 1.26; p = 0.74. Knowledge assessment: a mean difference in change from baseline = 1.58 (C-E); 97.5% CI: −0.58 to 3.75; p = 0.1. Although confidence and knowledge scores increased in both groups, the study cannot conclude non-inferiority. The trade-off between the inability to conclude efficacy of the impact of the website and the benefit of having an accessible educational platform on prone positioning and skin damage prevention makes the PRONEtect Education Hub an acceptable adjunct to traditional lecturing. •Education on prone positioning and skin/tissue damage was developed and evaluated.•The simulation videos and prone protocol were validated by international experts.•Knowledge scores and confidence levels increased in both groups.•The study could not conclude non-inferiority due to high attrition rates.•The PRONEtect Education Hub is an acceptable adjunct to traditional lecturing.