Background: Although dual antiplatelet therapy is the standard of care in non-ST-segment elevation acute coronary syndromes (NSTEACS), it remains unclear when a second antiplatelet agent should be initiated. We sought to assess the safety and efficacy of pre-treatment with clopidogrel in patients with NSTEACS undergoing percutaneous coronary intervention (PCI). Methods: We analysed baseline clinical and procedural characteristics of 6817 patients with NSTEACS who underwent PCI from the Melbourne Interventional Group registry from 2005 to 2012. Patients were included in the pre-treatment group if clopidogrel was administered prior to cardiac catheterisation. We assessed 30-day mortality, myocardial infarction (MI) and major adverse cardiovascular events. The safety endpoint was in-hospital bleeding. Results: Of the 6817 patients, only 2951 (43 ) received pre-treatment with clopidogrel. Patients in the pre-treatment group were more likely to present with unstable angina (70.8 vs 68.2 , P = 0.02) and have a history of MI (35.6 vs 23.6 , P <0.01) but were less likely to have PCI within 24 h of admission (17.2 vs 25.2 , P <0.01). There was no difference between the groups in 30-day mortality (0.9 vs 1.4 , P = 0.06), MI (2.0 vs 2.2 , P = 0.52) or major adverse cardiovascular event (3.7 vs 4.2 , P = 0.25). There was no difference in bleeding complications (1.9 vs 1.9 , P = 0.94). Conclusions: Pre-treatment with dual antiplatelet therapy in NSTEACS is not routine clinical practice in Australia. Pre-treatment appears safe but is not associated with improved short-term clinical outcomes.