OBJECTIVE: To describe barriers nurses experienced in providing safe practice in the neonatal intensive care unit and to investigate area of errors commonly affected when nurses confronted the barriers. DESIGN: Qualitative descriptive method. SETTING: Randomly selected 4 large neonatal intensive care units in Thailand. PARTICIPANTS: Twenty-seven neonatal intensive care unit nurses. MAIN OUTCOME MEASURES: A semistructured interview of the nurses' experience of neonatal intensive care unit error, factors forming barriers to safe practice, and neonatal outcome. RESULTS: Of 245 error events, neonates were identified to suffer 126 (55.5%) adverse events. Five themes emerged as common factors obstructing nurses from incorporating safety processes into their caring roles: human susceptibility to error, system operating care weakness, problematic medical devices, poor team communication, and situational provocation. Multiple barriers were largely associated with understaffing, a sudden increase in patient acuity, multiple assignments, and an inadequate knowledge of safety in neonatal critical care, which often interacted and influenced their performance when processed to a single error occurrence. CONCLUSION: A focus on management of the potential barriers in a system-related human error approach could prevent and intercept future errors in this vulnerable population.