The objective of the Study on Transitions in Employment, Ability and Motivation (STREAM) is to acquire knowledge on determinants of transitions in employment and work productivity among persons aged 45-64 years. Research Framework: A research framework was developed, in which transitions in employment (e.g. leaving the workforce, entering the workforce, job change) and work productivity are influenced by the following determinants: health, job characteristics, skills and knowledge, social factors, and financial factors. Central explanatory variables in the framework are the ability to work, the motivation to work, and the opportunity to work. Study Design: STREAM is a prospective cohort study among 12,055 employees, 1,029 self-employed persons, and 2,034 non-working persons, all aged 45 to 64 years at baseline. The study sample was stratified by age and employment status (employed, self-employed, non-working), and was drawn from an existing internet panel. The baseline measurement was carried out in 2010 (response: 70%), and with yearly follow-up measurements in 2011 (response: 82%), 2012 (response: 80%), and 2013. At each wave, participants fill out an online questionnaire covering all aspects of the research framework. Place and Duration of Study: The Netherlands, between October 2010 and December 2013. Methodology: Quantitative data on all aspects of the research framework were assessed with an online questionnaire, qualitative data were assessed with interview studies, and the questionnaire data can be linked to register data at Statistics Netherlands for 89% of the participants. Results: Transitions in employment between the first three waves of data among the participants are described. Conclusion: STREAM will provide insight in the determinants of healthy and productive labour participation among persons aged 45 years and older, which will support the development of interventions prolonging working life in good health, while maintaining good work productivity.