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The objective of this study was to investigate the associations between the neonatal intensive care unit (NICU) work environment, quality of care, safety, and patient outcomes. A secondary analysis was conducted of responses of 1247 NICU staff nurses in 171 hospitals to a large nurse survey. Better work environments were associated with lower odds of nurses reporting poor quality, safety, and outcomes. Improving the work environment may be a promising strategy to achieve safer settings for at-risk newborns.