Fatigue is a symptom of ACS, but it remains unclear who is at risk and what factors contribute to fatigue. The purpose of the systematic review was to identify factors that influence fatigue in patients with ACS. The review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Literature published from 1981 to 2017 was reviewed, and of 983 articles screened, 36 met inclusion criteria. Variables contributing to fatigue fell into 3 categories: demographic characteristics, clinical characteristics, and other factors. More fatigue was found in women than men, and significant differences in fatigue were identified by race. Additionally, sleep deprivation, depression, and anxiety were associated with higher levels of fatigue. The findings highlight the importance of demographic, clinical, and other factors' impact on fatigue in ACS patients. Fatigue is an important symptom in ACS and healthcare providers must recognize how patient variables affect symptom expression.