AIM: This aim of this study was to investigate the interactive effects of psychological empowerment and job satisfaction on the relationship between high-performance work systems (HPWS) and nurses' perceptions of the quality of patient care they provide. BACKGROUND: Studies of high-performing organizations in a variety of industries have consistently reported a positive relationship between HPWS and performance outcomes. Although many of these studies have been conducted in manufacturing, similar findings of a positive correlation between aspects of HPWS and improved patient outcomes have been reported in international health care studies. METHOD: We used regression analysis with tests of mediation and moderation to analyze survey responses collected in March 2008 of 201 nurses in a large regional Australian health service. FINDINGS: Psychological empowerment fully mediated the relationship between HPWS and perceptions of quality of patient care. Job satisfaction moderated the relationship between HPWS and perceptions of quality of patient care. CONCLUSION: Hospital managers should focus on promoting HPWS and ensuring that nurse unit managers have the competencies to empower and to enhance the job satisfaction of their staff.