Nurses' safety practices of medication administration, prevention of falls and unplanned extubations, and handover are essentials to patient safety. This study explored the prediction between such safety practices and work environment factors, workload, job satisfaction, and error-reporting culture of 1429 Taiwanese nurses. Nurses' job satisfaction, error-reporting culture, and one environmental factor of nursing quality were found to be major predictors of safety practices. The other environment factors related to professional development and participation in hospital affairs and nurses' workload had limited predictive effects on the safety practices. Increasing nurses' attention to patient safety by improving these predictors is recommended.