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We evaluated the clinical and economic impact of a multidisciplinary programme to reduce bleeding events in patients with acute coronary syndrome (ACS) through optimisation of antithrombotic therapy.We designed a pre–post quasi-experimental intervention study using a retrospective analysis in two cohorts. The first cohort was analysed to detect correctable measures contributing to bleeding (PRE, January–July 2010). Secondly, a bundle of interventions was implemented and thirdly, a second cohort of patients was evaluated to investigate the impact of our measures on bleeding reduction (POST: September 2011–February 2012). The impact on health outcomes was evaluated through comparison of the percentage of inhospital bleedings and 30 day readmissions between the two cohorts. The economic analysis took into account the costs associated with implementation of the programme and the cost savings associated with the prevention of bleedings.A total of 677 patients were included (377 in PRE and 300 in POST). The bundle of interventions consisted of:Overdose avoidance measures: the percentage of patients overdosed was reduced by 66.3% (p<0.001).Prescription of antithrombotic drugs with a more favourable bleeding profile: the percentage of patients treated with fondaparinux increased (2.4% vs 50.7%; p<0.001).Avoidance of combinations of antithrombotic agents with an increased risk of bleeding: only 1 patient in POST received abciximab plus bivalirudin (p=0.016).Mandatory measurement of body weight: the percentage of patients weighed was increased (67.4% vs 88.7%; p<0.001).The total bleeding rate was reduced after implementation of the interventions by 29.2% (31.6% vs 22.3%; OR 0.62; 95% CI 0.44–0.88) while 30 day readmission rates were 7.7% in PRE and 5% in POST (p=0.20). The estimated avoided cost was €95 113.6 per year, meaning that €10.1 would be obtained in return for each €1 invested during the first year and €36.3 during the following years.This multidisciplinary programme has proven to be effective in reducing bleeding events and is economically attractive.