Acute coronary syndrome (ACS) occurs as a result of myocardial ischemia that can give rise to a variety of acute cardiovascular events, including arrhythmia, heart failure and sudden cardiac death (SCD). Currently, there are challenges and insufficient innovations regarding early diagnosis and therapeutic approaches within ACS patients experiencing SCD. Plasma extracellular vesicles (EVs) might serve as biomarkers of many diseases depending on the biological molecules of their cargo, such as miRNAs. This study aims to identify the plasma EVs containing miRNAs as novel biomarkers for the prediction of SCD in ACS patients. A total of 39 ACS patients experiencing SCD and 39 healthy control individuals (HC) were enrolled, among which 9 samples in each group were randomly selected as testing groups for miRNA sequencing in plasma EVs, and the remaining samples were assigned to the validation group. The top 10 significant expression miRNAs were verified by the real-time quantitative polymerase chain reaction. Upregulation of miR-208b-3p, miR-143-3p, miR-145-3p and miR-152-3p, and down-regulation of miR-183-5p were further validated in the validation group. Spearman's correlation analysis and the receiver operating characteristic (ROC) curve showed that both miR-208b-3p and miR-143-3p levels were positively correlated with myoglobin (MYO), and their predictive power for SCD was confirmed. In conclusion, our findings indicate that plasma EVs miR-208b-3p and miR-143-3p may serve as promising biomarkers in predicting SCD in patients with ACS, as well as postmortem forensic diagnosis of the cause of death due to ACS.