Background/Aims: Antiplatelet therapy with aspirin and clopidogrel is an important component of the management of acute coronary syndrome, but it also increases the risk of bleeding. There are no formal guidelines about the use of a proton pump inhibitor (PPI) for gastroprotection in patients on clopidogrel. This study assessed how many patients in the Royal Darwin Hospital (RDH) and the Royal Hobart Hospital (RHH) prescribed clopidogrel and at risk of bleeding were co-prescribed PPIs. Methods: We conducted a retrospective cohort study using a pharmacy database to select all patients commenced on clopidogrel in a 1-year period. We identified all patients newly prescribed clopidogrel and determined the proportion that had a risk factor for bleeding and also received a PPI. We also assessed the effect of the use of PPIs on the number of reported bleeds. Results: The final study cohort consisted of 385 patients who had been newly prescribed clopidogrel. Of all patients discharged on clopidogrel, 95·6% (368/385) had ≥1 risk factor for bleeding. One hundred and twenty-eight of these patients [128/368, (34·8%)] were discharged on a PPI. Patients on dual antiplatelet therapy with an additional risk factor for bleeding and not discharged on a PPI were more likely to develop a major bleed than patients on dual antiplatelet therapy without a risk factor for bleeding not discharged on a PPI (11·1% vs. 1·8%; P < 0·01). Patients on dual antiplatelet therapy with an additional risk factor for bleeding not discharged on a PPI had a higher probability (borderline significance) of major bleeding, compared with patients on dual antiplatelet therapy with an additional risk factor for bleeding discharged on a PPI [PPI: 1/60, (1·7%) vs. no PPI: 6/54, (11·1%); P = 0·05]. Conclusions: Our results indicate that PPIs may only lower the probability of major bleeding in patients treated with dual antiplatelet therapy, who possess additional risk factor(s) for bleeding.