29 Background: The American Cancer Society estimated that 1.9 million new cancer cases were identified in 2021, comprising 260,210 newly diagnosed male genital neoplasm cases. Prostate cancer is considered the second leading cause of cancer-related mortality among men in the United States (US). Cardiovascular events are commonly observed in patients receiving androgen deprivation therapy or platinum-based chemotherapy, fundamental treatments for malignant male reproductive organ tumors. Therefore, the objective of our study is to evaluate the temporal and regional trends of cardiovascular mortality in men 55 years or older with malignant neoplasms of the male genital organs in the US from 1999 to 2020. Methods: We used the death certificate data from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database to determine crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) per 100,000 individuals. Joinpoint regression calculated the annual percent change (APC) and average annual percent change (AAPC) in AAMR. Results: A total of 109,970 cardiovascular-related deaths occurred in older adults with neoplasms of male genital organs in the US from 1999-2020, with an overall AAMR of 18.55. A gradually decreasing trend in mortality was observed until 2003 (APC -4.43, 95% CI = -5.33 to -3.16), followed by a sharp decline until 2013 (APC -6.89, 95% CI = -7.36 to -6.62), and another gradual decline till 2018 (APC -3.12, 95% CI = -4.21 to -1.99). However, from 2018 to 2020, a drastic increase was observed (APC 6.03, 95% CI = 3.41 to 7.96). Individuals older than 85 showed the highest mortality (130.17), followed by those aged 75 to 84 (31.79). Among racial groups, the highest AAMR was seen in Non-Hispanic (NH) Black or African Americans (33.87), followed by NH Whites (18.14), NH American Indians or Alaskan Natives (13.26), Hispanics (11.50), and NH Asians or Pacific Islanders (7.98). Among census regions, the highest and lowest mortality were observed in the Western region (20.04) and Southern region (16.34), respectively. While urban areas reported a significantly higher number of deaths (88,263) compared to rural areas, the AAMR was higher in rural areas (20.20) than in urban areas (18.16). Conclusions: An overall decreasing trend of cardiovascular mortality was observed among older adults with malignant neoplasms of male genital organs from 1999 to 2020 in the US; however, the sharp rise from 2018 to 2020 is important to consider. There were notable disparities in mortality among NH Blacks or African Americans, males over 85, and residents of rural and Western regions. The results of our study highlight the necessity of providing cardiovascular treatment to cancer patients at earlier stages, particularly in vulnerable subgroups, necessitating close collaboration between oncologists and cardiologists.