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Introduction: Morphine is endorsed by all acute coronary syndromes (ACS) guidelines. However, some mechanistic studies have demonstrated that morphine impairs absorption and blunts antiplatelet effect of oral ADP receptor blockers. The clinical relevance of this interaction is controversial. Hypothesis: If morphine delays ADP receptor blocker absorption and decreases the extent of platelet inhibition, then its concomitant use with clopidogrel may increase risk of short-term ischemic events. Methods: This is a post-hoc analysis from the EARLY-ACS trial, which randomized patients with non-ST elevation ACS (NSTEACS) within 24 hours of clinical presentation to early versus delayed provisional epitifibatide. We analyzed morphine use before randomization across two separate populations: those ones that were treated with clopidogrel before randomization (5,438 patients) and those ones that were not (3,462 patients). Outcomes of interest were the composite of death, myocardial infarction, recurrent ischemia with need for urgent revascularization or thrombotic bailout during percutaneous coronary intervention at 96 hours (the same one used for the main trial) and TIMI major or minor bleeding at 120 hours. An inverse probability of treatment weighting (IPTW) propensity score model was developed to adjust for confounders. Results: A total of 1,024 patients were treated with morphine before randomization and 7,876 were not. Patients taking morphine were more likely to have heart failure at baseline, to be on nitrates and to be enrolled in North America. Results for ischemic outcomes are described at Figure 1. There was no association of prior morphine use with bleeding (OR 1.1; 95 % CI 0.79 to 1.52 for the overall cohort). Conclusions: When used together with clopidogrel, NSTEACS patients who received morphine had higher risk of short-term ischemic events. On the other hand, there was no such association when clopidogrel was not given together with morphine. [ABSTRACT FROM AUTHOR]