Diaper dermatitis is a major issue among hospitalized infants, leading to increased medical costs, pain, risk for infection, and distress among patients and caregivers. An evidence-based algorithm for prevention and treatment of diaper dermatitis was developed and introduced in a level IV neonatal intensive care unit (NICU). Two cases are discussed as examples of severe diaper dermatitis. The first case demonstrates the final case of severe diaper dermatitis since the introduction of the algorithm. The second case demonstrates a less severe, but equally frustrating, case of diaper dermatitis that occurred after the practice of using the algorithm was established. The need for consistency in the prevention and treatment of diaper dermatitis is paramount to providing quality care. There are a number of points within the bedside care regimen where breakdown in consistency occurs. The adherence to consistent and evidence-based treatment regimens has the potential to decrease the incidence and severity of diaper dermatitis in high-risk hospitalized infants. Initiation of an evidence-based algorithm to assist in the prevention and treatment of diaper dermatitis can be supported by data of the number of cases of diaper dermatitis collected before and after implementing the algorithm. The information can further assist in continued education and pursuance of investigation of other major skin injuries in NICU patients. The importance surrounding infant skin care and building awareness surrounding all of the facets of skin care in this vulnerable population demonstrate the benefits to quality outcomes and care.