SummaryBackground: In the TARGET study, sub-optimal platelet inhibition with tirofiban was held responsible for the higher incidence of periprocedural CK-MB release compared to abciximab. Since then, a new, higher bolus dose of tirofiban has been proposed to increase blood concentrations very soon after the start of treatment.Objective: The aim of this study was to explore the bleeding risk and clinical outcome at 30 days in a series of patients undergoing percutaneous coronary intervention (PCI) with the new dosing regimen of tirofiban (25 μg/kg bolus followed by a 0.15 μgkg−1min−1 infusion for 18 h).Methods: A total of 133 consecutive patients underwent a PCI and received a high bolus dose of tirofiban. Platelet function inhibition was measured using the Ultegra™ RPFA (Accumetrics) 10 min and 8 and 24 h after the start of therapy in the first 38 cases.Results: The procedural success rate was 98.5%. The mean level of platelet inhibition 10 min after the start of therapy was 94.7 ± 5.9%. No major bleedings, no need for red blood cell transfusion and no episodes of severe thrombocytopoeniawere recorded. Groin haematoma was observed in seven patients (5.3%). The cumulative incidence of 30-day major adverse cardiovascular events was 4.6% (five myocardial infarctions and one repeat PTCA for sub-acute stent thrombosis).Conclusions: The use of a high bolus dose of tirofiban in patients undergoing PCI seems to be safe and not associated with an increased risk of major bleeding. This high bolus dose may help to further reduce the rate of periprocedural adverse events.