In the vast majority of cases, appropriate identification and mitigation of risk factors can prevent or minimize pressure ulcer (PU) formation. However, some PUs are unavoidable. Based on the importance of this topic and the lack of literature focused on PU unavoidability, the National Pressure Ulcer Advisory Panel hosted a multidisciplinary conference in 2014 to explore the issue of PU unavoidability within an organ system framework, which considered the complexities of nonmodifiable intrinsic and extrinsic risk factors. Prior to the conference, an extensive literature review was conducted to analyze and summarize the state of the science in the area of unavoidable PU development and items were developed. An interactive process was used to gain consensus based on these items among stakeholders of various organizations and audience members. Consensus was reached when 80% agreement was obtained. The group reached consensus that unavoidable PUs do occur. Consensus was also obtained in areas related to cardiopulmonary status, hemodynamic stability, impact of head-of-bed elevation, septic shock, body edema, burns, immobility, medical devices, spinal cord injury, terminal illness, and nutrition.