Background: Infection is the most important cause of non-relapse mortality in hematologic malignancy patients, leading to increased costs and prolonged hospitalization times. However, comprehensive and comparable reports on infection-specific mortality (ISM) trends in hematologic malignancy patients are lacking., Objectives: We aimed to provide updated ISM trends and factors associated with ISM among hematologic malignancy patients., Design: This is a retrospective study., Methods: Patients diagnosed with the five most common hematologic malignancies from 1983 to 2016 from the Surveillance, Epidemiology, and End Results database were included. Joinpoint regression was used to analyze mortality trends., Results: ISM decreased beginning in 1983, 1988, and 1994, with yearly decreases of -2.1% for acute leukemia (AL), -1.3% for Hodgkin lymphoma (HL), and -14.3% for non-Hodgkin lymphoma (NHL). In contrast, ISM in patients with chronic leukemia (CL) and multiple myeloma (MM) increased dramatically beginning in 2000, with yearly increases of 2.8% and 3.3%, respectively. ISM rates were higher in males than in females across all hematologic malignancy subtypes. The mortality trends significantly differed according to race, age, sex, and stage, which could help in further etiological investigations. Moreover, male sex, older age at diagnosis, black race, and unmarried status were poor prognostic factors for ISM across all hematologic malignancy subtypes., Conclusion: A promising downward trend in ISM in recent years occurred in patients with AL, HL, and NHL; however, ISM increased dramatically in patients with CL and MM. Our data suggest that risk assessment and careful infection monitoring are recommended for hematologic malignancy patients, particularly those with CL and MM., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)