The clinical outcomes in acute myocardial infarction (AMI) patients with Killip class 3 are often inconsistent with those in the literature, and the factors associated with poor outcomes have not been sufficiently investigated. The purpose of this study was to identify factors associated with in-hospital death in AMI patients with Killip class 3. We included 205 AMI patients with Killip class 3, and divided them into a survived group (n = 189) and in-hospital death group (n = 16). The primary objective was to identify factors associated with in-hospital death using multivariate analysis. Age was significantly younger in the survived group than in the in-hospital death group (73.1 ± 11.2 versus 83.2 ± 6.2 years, P < 0.001). Systolic blood pressure (SBP) was significantly higher in the survived group than in the in-hospital death group (150.0 ± 31.2 versus 124.8 ± 25.3 mmHg, P = 0.002). The prevalence of TIMI thrombus grade ≥ 2 was significantly greater in the in-hospital death group than in the survived group (56.3 versus 22.2%, P = 0.005). In multivariate logistic regression analysis, in-hospital death was significantly associated with age [odds ratio (OR) 1.168, 95% confidence interval (CI) 1.061-1.287, P = 0.002] and TIMI thrombus grade ≥ 2 (versus ≤ 1: OR 5.743, 95% CI 1.717-19.214, P = 0.005), and inversely associated with SBP on admission (per 10 mmHg increase: OR 0.764, 95% CI 0.613-0.953, P = 0.017). In conclusion, in-hospital death was associated with age and coronary thrombus burden, and was inversely associated with SBP on admission in patients with Killip class 3. It may be important to recognize these high risk features to improve the clinical outcomes of patients with Killip class 3.