Background: The potential utility of microRNAs (miRNAs) in the diagnosis, prognosis, and treatment of multiple disease states has been an area of great interest since their discovery. In patients with cardiovascular disease, there is a large pool of literature amassed from the last decade assessing their diagnostic and prognostic potential. This systematic review sought to determine whether existing literature supports the use of miRNAs as prognostic markers after an Acute Coronary Syndrome (ACS) presentation. Methods: A systematic review of published articles from 2005–2019 using MEDLINE and EMBASE databases was undertaken independently by two reviewers. Studies addressing prognosis in an ACS population yielded 32 studies and 2 systematic reviews. Results/conclusion: 23 prospective studies reported significant differences in miRNA levels and 16 compared the predictive power of miRNAs. The most common miRNAs assessed included miR-133a, -208b, -21, -1, -34a, -150, and -423, shown to be involved in cell differentiation, apoptosis, and angiogenesis. Barriers to the use of miRNAs as prognostic markers include bias in miRNA selection, small sample size, variable normalization of data, and adjustment for confounders. Therefore, findings from this systematic review do not support the use of miRNAs for prognostication post-ACS beyond traditional cardiovascular risk factors, existing risk scores, and stratifications tools.