Abstract Background Limited data are available regarding the cardiovascular outcome including bleeding of patients with history of cancer who develop acute myocardial infarction (AMI). Purpose The purpose of this study was to analyze the characteristics and clinical outcomes of patients following AMI according to the history of cancer in in a contemporary cohort. Methods Consecutive patients with spontaneous onset of AMI were enrolled between December 2015 and May 2017 at 50 institutions in the Japan AMI Registry (JAMIR), a multi-center, nationwide prospective registry. Patients were divided into 2 groups according to a history of cancer at admission for index AMI events. The outcomes of interest were all-cause death, major bleeding defined as BARC type 3 or 5, and composite ischemic events defined as cardiovascular death, myocardial infarction and ischemic stroke. These events were analyzed by the log-rank test, and Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model with adjustment for covariates such as age, sex, body weight, ST-elevation MI, use of anticoagulants, history of cerebrovascular disease, trans-radial approach procedure, Killip class ≥2, estimated glomerular filtration rate, and history of previous MI or percutaneous coronary intervention. Results A total of 3,411 AMI patients were enrolled, and followed for a median of 358 days. Among those, 292 patients (8.6%) had a history of cancer and they were older and had more comorbidities than those without (mean age [standard deviation], 76.0 [9.9] vs 67.4 [13.3]; P<0.001). They had a similar risk of composite ischemic events (adjusted HR [adjHR] 1.18 [95% CI 0.80–1.75], P=0.39), and major bleeding (adjHR 1.13 [95% CI 0.70–1.83], P=0.61) compared with those without, whereas were at higher risk for all-cause mortality (adjHR 1.64 [95% CI 1.16–2.32], P=0.005; Figure 1). While no between-group difference in cardiovascular death was observed, non-cardiovascular death and death due to cancer were higher in the cancer group than in the no-cancer group (adjHR 1.38 [95% CI 0.85–2.24], P=0.19; adjHR 2.05 [95% CI 1.24–3.39], P=0.005; adjHR 18.16 [95% CI 6.74–48.97], P<0.001, respectively). When further stratified by age, there was neither the difference in cardiovascular events nor bleeding events by the presence or absence of a history of cancer, whereas the difference in all-cause mortality became pronounced in the group aged<75 years but not in the group aged>75 years (adjHR 3.32 [1.88–5.85] and 1.26 [0.81–1.96], respectively; Figures 1 and 2). There was a significant interaction between caner and age (P for interaction=0.008). Conclusion The real-world multi-center database JAMIR demonstrated that a history of cancer was associated with increased mortality in AMI patients aged<75 years. These results might suggest the need for a multidisciplinary approach to improve the prognosis of younger AMI patients with a history of cancer.Figure 1Figure 2