Abstract Background Acute identification and treatment of myocardial infarction (MI) is crucial for survival. MI symptom presentation is typically characterized by chest pain. Regular use of opioids to relief pain of chronic diseases is common. However, it has not been investigated whether opioid administered prior to onset of MI is associated more with atypical presentation of ischemia compared to non-opioid users. Purpose To investigate if opioid therapy is associated with atypical symptoms of MI. Methods The study is registry-based. MI is defined as patients with the ICD-10 discharge diagnoses I20.0 and I21 as primary diagnosis <24 hours after a call to the Capital Emergency Medical Services, including the Emergency Number (1–1-2) and Out-of-hours Service (OOHS). MI patients with opioid treatment prior to onset of MI are compared with a control group of MI patients without opioid treatment. The primary symptom of MI is registered in calls to the Capital Emergency Medical Services, from 2014 to 2018. Opioid treatment includes opioid prescribed and picked up <30 days prior to onset of MI. Results In total, 866 MI patients with opioid treatment and 10,061 MI patients without opioid treatment were included. The median age was 72.0 vs 67.8 years, 50.5% vs 34.5% were women, 61.0% vs 54.7% called the Emergency Number (1–1-2), ischemic heart disease was present in 48.5% vs 34.3% and type 2 diabetes in 23.1% vs. 16.2%. Atypical symptoms of MI were associated with opioid treatment and most prevalent in calls to OOHS, in women and by higher age. Acute symptoms of MI are visualized in Figure 1 and 2. Conclusion Opioid treatment prior to onset of MI was associated with increased atypical symptoms of MI, especially dyspnea, and increased in calls to the OOHS, in women and by higher age. This might challenge the clinician in early diagnose of MI in patients with opioid treatment and thereby delay acute lifesaving treatment. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation