Background: The prevalence of acute coronary syndrome (ACS) continues to increase among young Chinese adults. Homocysteine (HCY) has been suggested as a crucial promoter of atherosclerosis leading to coronary artery disease (CAD). Yet, it remains uncertain whether HCY is associated with the ACS and the severity of coronary artery stenosis in very young adults.Methods: Very young patients (18-35years of age) diagnosed with ACS who underwent coronary angiography (CAG) at Anzhen Hospital between January 2013 and June 2019 were assigned to the ACS group. An equivalent age-matched population without CAD, as confirmed by CAG during the same period, was assigned to the non-CAD group. A serum HCY level>15µmol/L was defined as hyperhomocysteinemia (HHCY). The Gensini score assessed the severity of coronary artery stenosis.Results: A total of 1,103 participants, including 828 ACS patients and 275 non-CAD subjects, were included in this study. Very young ACS patients had higher level of serum HCY and greater prevalence of HHCY compared with non-CAD subjects [for HCY, 16.55 (11.93- 29.68) vs 12.50 (9.71- 17.42), P<0.001; for HHCY prevalence, 62.08% vs 26.18%, P<0.001]. Multivariate logistic regression analysis with the stepwise method indicated that HHCY was an independent predictor associated with the presence of ACS, after adjusting for traditional confounders (OR, 4.393; 95% CI, 3.171-6.087; P<0.001). Moreover, young ACS patients with HHCY had increased prevalence of ST-segment elevation myocardial infarction (STEMI) (P=0.041), multi-vessel disease (P=0.036), and decreased value of left ventricular ejection fraction (LVEF) (P=0.01). Also, the HCY level was significantly correlated with Gensini Score in ACS patients (r=0.142, P<0.001).Conclusion: HHCY was significantly associated with the presence of ACS and the severity of coronary artery stenosis in very young patients ≤35 years of age.