Background: Healthcare workers are at risk of blood and body fluid exposures (BBFE) while delivering care to patients. Despite recent technological advances such as safety-engineered devices (SEDs), these injuries continue to occur in healthcare facilities worldwide. Aims: To assess the impact of an education and SEDs workplace programme on rates of reported exposures. Methods: A retrospective cohort study, utilizing interrupted time series analysis to examine reported exposures between 2005 and 2015 at a 600-bed hospital in Perth, Western Australia. The hospital wards were divided into four cohorts. Results: A total of 2223 records were available for analysis. The intervention was most effective for the first cohort, with significant improvements both short-term (reduction of 12 (95% CI 7-17) incidents per 1000 full-time equivalent (FTE) hospital staff) and long-term (reduction of 2 (CI 0.6-4) incidents per 1000 FTE per year). Less significant or consistent impacts were observed for the other three cohorts. Overall, the intervention decreased BBFE exposure rates at the hospital level from 19 (CI 18-20) incidents per 1000 FTE pre-intervention to 11 (CI 10-12) incidents per 1000 FTE post-intervention, a 41% reduction. No exposures resulted in a blood-borne virus infection. Conclusions: The intervention was most effective in reducing exposures at a time when incidence rates were increasing. The overall effect was short-term and did not further reduce an already stabilized trend, which was likely due to improved safety awareness and practice, induced by the first cohort intervention.