BACKGROUND:Traditionally, opioids have been the analgesia of choice for patients with ST-Elevation Myocardial Infarction (STEMI). Recent studies, however, have raised the possibility of harmful effects of opioid administration through delayed onset of antiplatelet agents. OBJECTIVE:To perform a systematic review of the effects of parenteral opioids in patients presenting with STEMI. METHODS:Medical databases were systematically searched to 28 February 2018. Randomised control trials (RCTs) and observational studies were included if they interrogated the effects of parenteral opioids as compared to no opioid administration in STEMI patients. Outcomes included in-hospital, 30-day, one-year major adverse cardiac events (MACE) and platelet reactivity measures. The studies were evaluated using GRADE (Grade of Recommendation, Assessment, Development and Evaluation). RESULTS:One (1) RCT and 17 non-randomised, non-controlled observational studies were identified. The only RCT was of high quality, but only evaluated the pharmacokinetics of STEMI patients and had a small sample size. The remaining studies were of low-moderate quality, mainly due to eligibility criteria and confounding. Most studies report higher platelet reactivity with opioids, but clinical outcomes (MACE) were equivocal. CONCLUSION:This systematic review highlights the paucity of quality research evaluating the effect of opioids on its clinical and pharmacological effect on STEMI patients. Current literature indicates that opioids are associated with prolonged platelet reactivity. Whether this affects clinical outcomes remains to be established. Given the widespread use of opioids in STEMI, there is an urgent need for adequately powered trials investigating their safety.