In view of hemorrhagic and prothrombotic tendencies, ST-segment elevation myocardial infarction (STEMI) patients with chronic hematologic malignancies (CHM) are felt to be at a higher risk and hence denied standard reperfusion strategies. In-hospital outcomes of CHM patients presenting with STEMI are unclear. The Nationwide Inpatient Sample data files from 2003 to 2014 were used to extract adult patients who presented with a primary diagnosis of STEMI. Patients who had a diagnosis of CHM defined as chronic myelogenous leukemia, chronic lymphocytic leukemia, essential thrombocythemia, polycythemia vera, chronic monocytic leukemia, and multiple myeloma were identified. The primary study outcome measure was in-hospital mortality. Inverse probability weighting-adjusted binary logistic regression was performed to identify independent predictors of in-hospital mortality. Of 2,715,807 STEMI patients included in the final analyses, 11,974 (0.4%) patients had a diagnosis of CHM. Patients with CHM were significantly older, had a higher prevalence of co-morbidities, and had a significantly higher unadjusted in-hospital mortality (14.9% vs 9.0%; p <0.001). After adjusting for co-morbidities, CHM did not independently predict a higher in-hospital mortality (odds ratio = 1.02, 95% confidence interval = 0.96 to 1.09; p = 0.461). In patients with CHM who presented with STEMI, percutaneous coronary intervention was found to be associated with a significant reduction in in-hospital mortality (odds ratio = 0.22, 95% confidence interval = 0.18 to 0.27; p <0.001) (c-statistic = 0.81). In conclusion, CHM patients presenting with STEMI should be treated with similar treatment strategies as those without CHM, including revascularization if indicated, as there appears to be a sizable outcome advantage with this approach.