A new, synthetic, silk-like fabric was developed for the purpose of providing bedding and patient gowns that manage moisture, friction, and shear when used between the patient and the healthcare support surface that may affect the development of pressure ulcers (PUs). A retrospective study was conducted to compare the incidence of hospital-acquired PUs in patients admitted to Telemetry, Urology, and Intensive Care Units before and after hospital linens were changed from standard to the synthetic (intervention) linens. Patient medical record data were abstracted for a period 12 weeks before (control) and 12 weeks following the linen change (intervention). Patient demographic information, Braden Risk Scale score, and PU status and stage were abstracted for a total of 659 patients in the control and 768 patients in the intervention groups. No significant differences in patient weight, age, gender distribution, PU risk (Braden scale scores), or proportion of PUs on admission between groups were found. The most common comorbidity was hypertension (n = 981, 68.7%). On admission, the percentage of patients with PUs in the control and intervention groups was 9.9% (σ = 0.3) and 8.7% (σ = 0.3), respectively (P = 0.23). Average length of stay was 5.6 days in the control and 5.2 days in the intervention groups (P = 0.08). Sixty-eight (68) of 659 patients (10.3%) in the control and 19 out of 768 patients in the intervention group (2.5%) developed one or more PUs (P <0.001) for an incidence of 11.5% in the control and 3.1% in the intervention group. At discharge, 136 PUs were present in the control and 64 were present in the intervention group (P <0.001). The significant differences in the incidence of hospital-acquired PUs between the two groups suggest that linen type affects PU risk. Additional controlled clinical studies in high-risk patient populations are warranted.