Objective: Characterization of a non-invasive method of quantifying subepidermal moisture (SEM) surrounding stages III and IV pressure ulcers (PrUs) in spinal cord injury (SCI). Design: Prospective, single-visit, single-rater, observational study, using repeated-measures analysis. Method: Setting-inpatient units of one VA SCI Center. Participants: Convenience sample of 16 subjects with SCI with stage III or IV PrUs over sacrum or ischium. Interventions: Measurement with the MoistureMeter-D, a hand-held device using 300 MHz electromagnetic waves. Outcome measures: Dielectric constant, a dimensionless number which increases with the moisture content. Each subject had a PrU site and a control site. Measurements were made at each site, on intact skin, at four points spaced angularly around the site, in triplicate. Results: (1) Short-term, single-rater relative error was 2.5%. (2) Order effect: first readings were higher than second readings in 55 of 64 measurement sets. Order effect was significant for control sites (P < 0.0001) but not for PrU sites. (3) Angular effect: SEM varied by angle at the PrU sites (P < 0.01); 12 o'clock position the highest and 6 o'clock the lowest. (4) Ability to differentiate PrUs from intact skin: SEM at PrU sites was greater by 9.0% than control sites (P < 0.05). (5) Site effect: SEM was higher at sacral locations than ischial at control sites by 20% (P < 0.005). Conclusions: SEM differentiates PrUs from intact skin. Future study designs must take into account order, angular, and site effects on this measure. This information will inform designers of future studies of SEM in healing of PrUs.