A substantial body of research has investigated the effects of work on the psychological well-being of employees. However, there has been little assessment of the ways in which workplace factors (such as job demands, working conditions, inter-personal relations and workplace change) interact with personal factors (such as work-life balance, family circumstances, key personality traits or demographic characteristics) to affect psychological health. This article reports findings from a study which aimed to construct and test a comprehensive model of the influences on employee well-being within the UK National Health Service (NHS). The results show that psychological well-being is influenced by a complex array of personal, environmental and work factors. A key finding is that there are clear associations between workplace change and well-being and between work-life (im)balance and well-being. These effects appear to be independent of one another and therefore require separate attention from managers and employers.