This study is intended to improve understanding of the impact of workplace change on employee mental health and well-being. We construct and test a comprehensive measure of organizational change, which is then applied in a prospective longitudinal study of nearly 5400 employees in six UK National Health Service Trusts. Self-rated mental health was assessed using the 12-item version of the General Health Questionnaire (GHQ). Just under a quarter of the sample were at increased risk of psychiatric morbidity ('cases'). After controlling for a wide range of personal characteristics and work variables, it was found that respondents who reported an increase in the amount of work over the previous year were more likely to be classed as GHQ cases, whereas increased training and promotion and improved job security had a beneficial effect on employee mental health (less likelihood of being GHQ cases). Quantity or degree of change showed a somewhat ambiguous relationship with GHQ status. Our findings challenge the assumption that change will necessarily have an adverse effect on health, indicating areas, such as promotion and development, where a positive impact might be anticipated.