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Eighteen years ago, the Institute of Medicine estimated that medical errors in hospital were a major cause of mortality. Since that time, reducing patient harm and improving the culture of patient safety have been national health care priorities. The study objectives were to describe the current state of patient safety in pediatric acute care settings and to assess whether modifiable features of organizations are associated with better safety culture.An observational cross-sectional study used 2015–2016 survey data on 177 hospitals in four U.S. states, including pediatric care in general hospitals and freestanding children's hospitals. Pediatric registered nurses providing direct patient care assessed hospital safety and the clinical work environment. Safety was measured by items from the Agency for Healthcare Research and Quality's Culture of Patient Safety survey. Hospital clinical work environment was measured by the National Quality Forum-endorsed Practice Environment Scale.A total of 1875 pediatric nurses provided an assessment of safety in their hospitals. Sixty percent of pediatric nurses gave their hospitals less than an excellent grade on patient safety; significant variation across hospitals was observed. In the average hospital, 46% of nurses report that mistakes are held against them and 28% do not feel safe questioning authority regarding unsafe practices. Hospitals with better clinical work environments received better patient safety grades.The culture of patient safety varies across U.S. hospital pediatric settings. In better clinical work environments, nurses report more positive safety culture and higher safety grades.