Background: Nurse practitioners (NPs) play an important role in addressing growing health care needs. Among NPs, organizational empowerment is positively associated with overall practice outcomes. Therefore, efforts to promote organizational empowerment in practice are necessary to increase job satisfaction among NPs as well as decrease the stress and intention to leave. Purpose: This study investigated the relationships of organizational empowerment and practice outcomes of job satisfaction, work stress, and intention to leave in acute care practices. Methodological orientation: This study was conducted as a cross-sectional design with a national survey of 946 acute care NPs. Questionnaires contained demographic and practice characteristics, Misener Nurse Practitioner Job Satisfaction Scale, Condition for Work Effectiveness Questionnaire II, and the work stress VAS scale. Hierarchical Linear Model (HLM) was used to investigate individual NP-level or organization-level effects on job satisfaction. The factors associated with job satisfaction were examined by stepwise multiple regression. Results: The organizational empowerment was low, work stress was moderately high, and job satisfaction was between slightly unsatisfied and slightly satisfied. The HLM results indicated that organization-level effects did not affect the job satisfaction of NPs. Nurse practitioners with greater formal power, resources, and informal power had higher job satisfaction. Conversely, NPs with an intention to leave and a higher level of stress showed lower job satisfaction. Conclusions: Organizational empowerment, intention to leave, and stress affect job satisfaction of acute care NPs in Taiwan. Implications for practic: To enhance the job satisfaction of NPs, health care administrators should empower NPs by providing access to opportunity, support, information, and resources in the health care delivery system.