Abstract Pressure injuries (PrIs), commonly located over bony prominences, are local areas of damage to the skin and underlying soft tissue caused by pressure and shear forces. These painful, dangerous, costly, and preventable injuries in nursing home (NH) residents are associated with reduced quality of life and mortality. This embedded pragmatic stepped wedge cluster clinical trial, using a mixed-methods approach for all residents in 8 NHs, will examine use of subepidermal moisture (SEM) assessment results as a cue for nursing staff to initiate PrI prevention. SEM assessment, a biophysical measure that senses changes in skin characteristics, detects early pressure damage by identifying subclinical signs of PrI. SEM use is an innovative addition to current PrI prevention care that is currently initiated upon a positive risk assessment and/or a visual inspection of skin discoloration. Significant damage exists by the time erythema or purple skin is observed. Lag time between pressure-induced tissue damage and visual detection of skin discoloration delays nursing actions to prevent PrIs. Discoloration is more difficult to discern in persons with dark skin tones, making skin damage detection more challenging for residents from minority or under-represented racial/ethnic groups than those with lighter skin tones; thus, producing a health disparity. The study will incorporate SEM assessment into PrI prevention standard-of-care and conduct the intervention over a 9-month period. The study aims are to: 1) determine if early pressure damage detected by SEM assessment at time of visual skin observation of NH resident sacral and heel areas is effective in cueing initiation of NH standard PrI prevention; 2) examine the association between NH standard PrI prevention and SEM assessment and NH residents’ characteristics (age, gender, risk, skin tone, race, ethnicity, BMI, cognitive status) and their interactions on individual NH residents with regard to initiation of NH standard PrI prevention and PrI occurrence; and, 3) explore if SEM usability, NH, and nursing staff characteristics influence the adoption and assimilation of early PrI detection and subsequent PrI prevention practices. Current NH PrI prevention protocols and periodic safety and care checks will be performed. Sample will be comprised of all residents at intervention start and those newly admitted during the 9-month intervention period. An intention to treat approach will be used for quantitative analyses with resident data accrued throughout the intervention period included in analyses. Cueing effectiveness will be determined by evaluating the initiation of PrI prevention strategies in relation to SEM values and the development of PrI during the intervention. Mixed effects regression models for clustered/repeated measures will use electronic health record data and SEM assessment values modeled to predict initiation of PrI prevention actions. Qualitative analyses will be applied to focus group ...