Objectives: To investigate the effects of a multifaceted implementation strategy on behaviour, behavioural determinants, knowledge and awareness of healthcare workers regarding the use of recommendations to prevent hand eczema. Methods: The Hands4U study is a randomised controlled trial. A total of 48 departments (n=1649 workers) were randomly allocated to the multifaceted implementation strategy or the control group (minimal implementation strategy). Within the departments designated to the multifaceted implementation strategy, participatory working groups were set up to enhance the implementation of the recommendations for hand eczema. In addition, working group members were trained to become role models, and an education session was given within the department. Outcome measures were awareness, knowledge, receiving information, behaviour and behavioural determinants. Data were collected at baseline, with a 3- and 6-month follow-up. Results: Statistically significant effects were found after 6 months for awareness (OR 6.30; 95% CI 3.41 to 11.63), knowledge (B 0.74; 95% CI 0.54 to 0.95), receiving information (OR 9.81; 95% CI 5.60 to 17.18), washing hands (B -0.40; 95% -0.51 to -0.29), use of moisturiser (B 0.29; 95% CI 0.20 to 0.38), cotton under gloves (OR 3.94; 95% CI 2.04 to 7.60) and the overall compliance measure (B 0.14; 95% CI 0.02 to 0.26), as a result of the multifaceted implementation strategy. No effects were found for behavioural determinants. Conclusions: The multifaceted implementation strategy can be used in healthcare settings to enhance the implementation of recommendations for the prevention of hand eczema. Trial registration number NTR2812.