Background: As an alternative method to evaluate insulin resistance (IR), triglyceride-glucose index (TyG) was shown to be related to the severity and prognosis of cardiovascular diseases. The main aim of this study was to explore the association between TyG and in-hospital mortality in critically ill patients with heart disease. Method: The calculation method of TyG has been confirmed in previous report: Ln [fasting TGs (mg/dL) \times FBG (mg/dL)/2]. All patients were divided into four different categories according to TyG quartiles. Primary outcome was in-hospital mortality. Binary logistic regression analysis was performed to determine the independent effect of TyG. Result: 4839 critically ill patients with heart disease were involved. The overall mortality was 8.53 cases per 100 idviduals. In-hospital mortality increased as TyG quartiles increased (Quartile 4 vs Quartile 1: 12.1 vs 5.3, p 0.001). Even after adjusting for confounding variables, TyG was still independently associated with the increased risk of in-hospital mortality in critically ill patients with heart disease (Quartile 4 vs Quartile 1: OR (95% CI): 1.83 (1.27, 2.64), p 0.001, P for trend 0.001). In the subgroup analysis, we failed to observe the association between increased TyG and the risk of mortality in patients complicated by diabetes. In addition, as TyG quartiles increased, the length of intensive care unit (ICU) stay was prolonged (Quartile 4 vs Quartile 1: 2.3 (1.3, 4.9) vs 2.1 (1.3, 3.8), p = 0.007). And the significant interactions were not found in most subgroups. Conclusions: TyG was independently correlated with in-hospital mortality in critically ill patients with heart disease.