The purpose of this study was to investigate the cause of death in subjects with α-synucleinopathies (ASs) and the confirmed presence of cardiac α-synuclein (α-syn), compared to non-AS disorders in a neuropathologically confirmed cohort. In total, 78 neuropathologically confirmed AS cases positive for cardiac α-syn were included in the study. Individuals with other neurocognitive diseases, having no α-syn in the brainstem or above, nor in cardiac nerves, served as controls (n = 53). Data regarding the cause of death, cardiac α-syn, pathological cardiac findings, and cardio- and cerebrovascular disease were assembled from autopsy reports and medical records. In the AS group, there was a significantly higher prevalence of sudden cardiac death ([SCD]; n = 40, 51.3%) compared to the control group (n = 12, 22.6%, p < 0.001). No statistically significant differences between the groups were reported regarding other cardiac conditions on autopsy or regarding cardio- and cerebrovascular disease from the medical records. The most prevalent cause of death in the AS group was SCD, which differed significantly from the control group. This suggests that α-syn deposits in cardiac nerves may cause lethal alterations in cardiac function, warranting further research.