Introduction: ST-elevation myocardial infarction (STEMI) presenting to the ED is a significant health burden. The provision of IV morphine with doses titrated to provide comfort is recommended in the AHA STEMI Guidelines, yet there is limited evidence of safety in this setting. The primary objective of this study was to measure potential harm associated with the provision of IV morphine in STEMI patients presenting to the ED. Methods: This was a two centre retrospective chart review from an urban, inner city, academic ED with an annual census of 85,000 visits, and an affiliated community hospital with 35,000 annual visits. Consecutive patients from April 2009 to January 2015 presenting to the 2 EDs with a diagnosis of STEMI were identified in the ED database. Eight trained research assistants, blinded to the study hypothesis, used standardized data collection templates. The primary investigator double collected 20% of all data to ensure completeness and accuracy. Results: We included 311 patients with STEMI (124 received morphine [M]; 187 no morphine [nM]). The ages of the two groups were similar (mean 64 yrs [M] & 67 yrs [nM]; median 63 yrs [M] & 66 yrs [nM]; IQR 45-81 [M] and 45.5-86.5 [nM]); as were the proportion of female patients (21.0% [M] & 23.5% [nM]. The pre-STEMI Charlson comorbidity scores (mean 2.6), median time to first ECG (11 min [M] & 16 min [nM]), and mean time-to-needle for PCI (96.8 min [M] & 92.0 min [nM]) were similar between groups. The mean CCU length of stay (LOS) (9.3 days vs 6.3 days) and hospital LOS (7.4 days vs 4.6 days) were longer for patients receiving morphine than those not receiving morphine. Rates of congestive heart failure, acute kidney injury and cardiac arrest in hospital were unchanged between the groups. Unadjusted mortality was similar (10.5% [M] vs 13.3% [nM]) between groups. Binary logistic regression controlling for age, Charlson score, first and peak troponin values demonstrated an association between receiving morphine in the ED and an increased risk of death at 30 days (OR 8.1; 95% CI 7.1.-9.1). Conclusion: The provision of morphine to patients with STEMI in the ED may be associated with increased CCU and hospital LOS. When controlling for age, pre-STEMI Charlson score, first and peak troponin values, receiving morphine was associated with an increased risk of death at 30 days. Further research to elucidate this association is warranted.