Significant variations and inconsistency in both the physician's and nurse's approach to the treatment of neonates with a "rule-out sepsis" (R/O sepsis) diagnosis is seen as both high cost and low quality. Because R/O sepsis is seen as a diagnostic dilemma for practicing clinicians, there has been a widespread tendency to readily initiate antibiotic treatment, without adequate consideration of the high financial and morbidity costs associated with the complications of treating the noninfected infant. This study demonstrates that the use of an agreed upon risk profile facilitated the collaborative standardization of diagnosis and treatment of the R/O sepsis patient, improved quality, and reduced costs (by minimizing over treatment) without increasing risk. This collaborative approach enhanced nurse-physician relationships, resulting in significant cost savings as well as diminished anxiety and confusion among the parents of neonates diagnosed with R/O sepsis.