BACKGROUND: Patients in hospitals and nursing homes are at risk for the development of often preventable adverse events. Guidelines for the prevention of many types of adverse events are available, however compliance with these guidelines appears to be lacking. As a result many patients do not receive appropriate care. We developed a patient safety program that allows organisations to implement multiple guidelines simultaneously and therefore facilitates guideline use to improve patient safety. This program was developed for three frequently occurring nursing care related adverse events: pressure ulcers, urinary tract infections and falls. For the implementation of this program we developed educational activities for nurses as a main implementation strategy. OBJECTIVES: The aim of this study is to describe the effect of interactive and tailored education on the knowledge levels of nurses. DESIGN: A cluster randomised trial was conducted between September 2006 and July 2008. SETTINGS: Ten hospital wards and ten nursing home wards participated in this study. Prior to baseline, randomisation of the wards to an intervention or control group was stratified for centre and type of ward. PARTICIPANTS: All nurses from participating wards. METHODS: A knowledge test measured nurses' knowledge on the prevention of pressure ulcers, urinary tract infections and falls, during baseline en follow-up. The results were analysed for hospitals and nursing homes separately. RESULTS: After correction for baseline, the mean difference between the intervention and the control group on hospital nurses' knowledge on the prevention of the three adverse events was 0.19 points on a zero to ten scale (95% CI: -0.03 to 0.42), in favour of the intervention group. There was a statistically significant effect on knowledge of pressure ulcers, with an improved mean mark of 0.45 points (95% CI: 0.10-0.81). For the other two topics there was no statistically significant effect. Nursing home nurses' knowledge did neither improve (0 points, CI: -0.35 to 0.35) overall, nor for the separate subjects. CONCLUSION: The educational intervention improved hospital nurses' knowledge on the prevention of pressure ulcers only. More research on long term improvement of knowledge is needed.