Background: Monocyte to high-density lipoprotein ratio (MHR) was a recently emerged lipid biomarker, might reflect the inflammation level and the lipid profile in a quantitative manner.We aimed to investigate the association of MHR with the severity of coronary artery disease (CAD), and the ability of MHR in predicting severe CAD and acute atherothrombosis events. Methods: A total of 3930 CAD patients and 1020 non-CAD patients presented consecutively to our hospital for coronary angiography. The CAD patients were classified into four groups according to the quartile of the MHR (≤0.28, N=1218; 0.28-0.39, N=1262; 0.39-0.53, N=1209; >0.53, N=1261). CAD severity was quantified according to the Gensini score. A receiver operating characteristic (ROC) curve analysis was also performed to predict severe CAD and acute coronary thrombotic events. Results: MHR was significantly higher in the CAD group than in the non-CAD group (0.45 ± 0.22 vs. 0.35 ± 0.17, p<0.001) and had a significant positive correlation with Gensini score. Compared with lower MHR value, a MHR in the fourth quartile was strongly associated with severe CAD and acute coronary thrombotic event after adjusting for baseline factors. Receiver-operating characteristic (ROC) curve analysis showed that combination of MHR and traditional risk predictors could better predict severe CAD especially acute coronary thrombosis events such as non-ST-elevation myocardial infarction (NSTEMI) and acute ST-segment elevation myocardial infarction (ASTEMI). Conclusions: MHR was positive associated with the prevalence and severity of CAD. Moreover, MHR may be a prognostic marker for acute atherothrombosis events.