Despite significant national progress in reducing central line-associated blood stream infection (CLABSI) rates, CLABSI remains a leading cause of preventable healthcare-associated harm in American neonatal intensive care units (NICUs). Most CLABSIs occur after central line insertion during the maintenance phase when central lines are frequently accessed by nurses for intravenous medication administration (IVMA). CLABSIs are mostly preventable when nurses reliably adhere to standardized care processes such as central line maintenance guidelines, yet NICUs report difficulty sustaining guideline adherence. Current approaches to increasing adherence focus on improving individual clinician performance, although such approaches are not effective for sustaining guideline adherence over time. An alternative approach is necessary to sustain CLABSI reductions made through quality improvement efforts. We propose to rigorously identify hazards and assess risks associated with NICU nurses' adherence to CLABSI and IVMA guidelines. We will take a human factors engineering approach and use the Systems Engineering Initiative for Patient Safety (SEIPS) model of work system and patient safety to conduct a prospective risk assessment of guideline adherence. The specific aims of the study are to 1) Identify hazards in the NICU work system that threaten nurses' adherence to CLABSI and IVMA guidelines and 2) Assess risk of potential failure modes associated with guideline adherence. We will employ both qualitative and quantitative data collection methods to achieve the aims including direct observations, interviews, Healthcare Failures Modes and Effects Analysis, and focus groups conducted with nurses who provide direct patient care in the NICU. This study is relevant to the public's health because it will increase our understanding of how factors in the NICU work system (technologies, tasks, the environment) influence nurses' adherence (and non-adherence) to guidelines intended to prevent hospital-acquired infections and IVMA-related errors. The results of this project will directly inform interventions to improve guideline adherence in the NICU and enhance neonatal patient safety.