PurposeTo explore the impact of chemotherapy on the risk of cardiac-related death in astrocytoma patients.MethodsWe retrospectively evaluated astrocytoma patients diagnosed between 1,975 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Using Cox proportional hazards models, we compared the risks of cardiac-related death between a chemotherapy group and non-chemotherapy group. Competing-risks regression analyses were used to evaluate the difference in cardiac-related death. Also, propensity score matching (PSM) was employed to reduce confounding bias. The robustness of these findings was evaluated by sensitivity analysis, and E values were calculated.ResultsA total of 14,834 patients diagnosed with astrocytoma were included. Chemotherapy (HR = 0.625, 95%CI: 0.444–0.881) was associated with cardiac-related death in univariate Cox regression analysis. Chemotherapy was an independent prognostic factor for a lower risk of cardiac-related death before (HR = 0.579, 95%CI: 0.409–0.82,P= 0.002) and after PSM (HR = 0.550, 95%CI: 0.367–0.823P= 0.004). Sensitivity analysis determined that the E-value of chemotherapy was 2.848 and 3.038 before and after PSM.ConclusionsChemotherapy did not increase the risk of cardiac-related death in astrocytoma patients. This study highlights that cardio–oncology teams should provide comprehensive care and long-term monitoring for cancer patients, especially those with an increased risk of cardiovascular disease.