Advances in screening technology have led to rapid expansion of newborn screening as a public health initiative in the United States.  Due to variation across states in program implementation, there is a lack of standardization and accountability, which can affect quality of care.  Texas currently screens for 28 disorders. OBJECTIVES: The Texas Newborn Screening Performance Measures Project was initiated with the objective of developing evidence-based performance measures to improve quality, accountability and uniformity in the care. METHODS: A three step approach was used for identification and development of key measures for 7 most critical disorders: systematic reviews; impact assessment; and feasibility assessment.  Impact assessments (likert scale) were based on National Quality Measures Clearinghouse™ (NQMC) criteria: scientific soundness, relevance, health importance,  impact on quality of care, and ability to address disparities in care.   A likert scale was also used for feasibility assessment on key aspects: data availability, ease of collection, infrastructure and human resource needs, overall cost, and time constraints.  RESULTS: A total of 50 performance measures were supported by scientific evidence.  Impact and feasibility assessments led to the approval of 33/50 measures.  “Time to initiate treatment” received the highest scores on potential impact on patient outcomes (mean impact score 86.67/100, SD 1.5).  Other measures with potentially high impact (score >80/100) were: compliance with oral prophylactic medication and age at first Prevnar® vaccination in sickle cell disease; screening of at-risk family members in fatty acid disorders; frequency of growth assessments in congenital adrenal hyperplasia and phenylalanine levels in phenylketonuria.  “Time to treatment” for individual disorders was also ranked very high on feasibility (mean feasibility score 88.67/100, SD 3.88). CONCLUSIONS:   This is one of the first efforts to identify and develop evidence-based performance measures in newborn screening and can pave the way for system wide changes and development of national guidelines.