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Abstract Background Cognitively straining conditions such as disruptions, interruptions, and information overload are related to impaired task performance and diminished well-being at work. It is therefore essential that we reduce their harmful consequences to individual employees and organizations. Our intervention study implements practices for managing the cognitive strain typical to office work tasks and working conditions in offices. We will examine the effects of a cognitive ergonomics intervention on working conditions, workflow, well-being, and productivity. Methods/design The study is a stratified cluster randomized trial. The clusters are work units, for example, teams or offices. The four participating organizations entered a total of 36 clusters, and we invited all 1169 knowledge employees of these units to participate. We randomly allocated the clusters into an intervention group (cognitive ergonomics) or an active control group (recovery supporting). We invited an additional 471 participants to join a passive control group only for baseline and follow-up measurements, with no intervention. The study consists of a baseline survey and interviews and observations at the workplace, followed by an intervention. It starts with a workshop defining the specific actions for the intervention implementation stage, during which we send task reminder questionnaires to all employees to support behaviour change at the individual and team levels. The primary outcome measure is perceived frequency of cognitive strain from working conditions; the secondary outcome measures include subjective cognitive load, well-being, workflow/productivity, and cognitive stress symptoms. Process evaluation uses the quantitative and qualitative data obtained during the implementation and evaluation phases. The baseline measurements, intervention phase, and end-of-treatment measurements are now complete, and follow-up will continue until November 2019. Discussion There is a need to expand the research of cognitive strain, which poses a considerable risk to work performance and employee well-being in cognitively demanding tasks. Our study will provide new information about factors that contribute to such strain. Most importantly, the results will show which evidence-based cognitive ergonomic practices support work performance in knowledge work, and the project will provide concrete examples of how to improve at work. Trial registration ClinicalTrials.gov, NCT03573674. Registered 29 June 2018.