Compared to acute myocardial infarction (AMI) with single vessel disease (SVD) or double vessel disease (DVD), AMI with triple vessel disease (TVD) is associated with higher mortality. The aim of this study was to identify the determinants of in-hospital death in AMI with TVD. We identified AMI patients with TVD in our tertiary medical center between January 2009 and December 2014. Baseline patient characteristics including laboratory data, echocardiograms, and coronary angiograms were collected from our hospital records. We divided our study population into a survivor group and non-survivor group. Multivariate stepwise logistic regression analysis was performed to identify the determinants of in-hospital death. A total of 138 AMI patients with TVD were identified and included as the final study population. Fifteen patients died during the hospitalization (mortality rate, 10.9%). Mean systolic blood pressure (134 ± 27 mmHg) was significantly greater in the survivor group compared with the non-survivor group (114 ± 31 mmHg) (P = 0.02). The prevalence of shock on admission was significantly less in the survivor group (15.4%) than in the non-survivor group (66.7%) (P < 0.001). Multivariate stepwise logistic regression analysis revealed that shock status on admission (OR 11.50, 95% CI 3.21-41.14, P < 0.001), the left anterior descending artery (LAD) as the infarct related artery (IRA) (OR 3.83, 95% CI 1.04-14.09, P = 0.04), and serum albumin on admission (OR 0.26, 95% CI 0.08-0.84, P = 0.02) were significantly associated with in-hospital death. In conclusion, shock status on admission, the LAD as the IRA, and a low serum albumin level were the determinants of in-hospital death in AMI patients with TVD.