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The aim of the present study was to investigate which hospital, unit and individual characteristics predict job satisfaction in four age cohorts of registered nurses (RNs).Adequate supply of direct care nurses in hospitals is paramount to the provision of safe patient care. While recruitment is important, interventions to retain experienced nurses in the work force should also be undertaken.Cross-sectional survey data from the 2004 National Database of Nursing Quality Indicators® (NDNQI®) RN Survey with Job Satisfaction Scales© were used. The sample included 53 851 RNs age 20–59 years divided into four age cohorts. Data were analysed using three-level hierarchical linear modelling.Overtime demand and involuntary floating resulted in significantly lower job satisfaction in all age cohorts. The oldest two cohorts reported higher job satisfaction with increased unit tenure whereas the youngest cohort reported decreased job satisfaction with increased unit tenure. Higher job satisfaction was reported in all cohorts within Magnet hospitals; however, the relationship was only significant in 40–49 year olds.Some factors are associated with job satisfaction in all age cohorts. Other factors differentially influence job satisfaction based on the cohort group.Nurse leaders should consider retention strategies congruent with the job satisfaction predictors of different age groups.