Senile systemic amyloidosis (SSA) features cardiomyopathy resulting from amyloid deposits of wild-type transthyretin (TTR). From 1994 to 2009, 82 patients with SSA were diagnosed at our center; 79 were men (96%) and median age at diagnosis was 73.8 years (range, 59.1–86.0). Most patients (77/78) presented with abnormal echocardiography; median values for interventricular septal thickness and left ventricular ejection fraction were 16 mm (range, 9–24) and 50% (range, 20–70), respectively. Fat aspirates were positive for amyloid in 27% of patients. Mean levels of brain natriuretic peptide (n = 41) and troponin I (n = 19) were 422 ± 279 pg/ml and 0.151 ± 0.107 pg/ml. Median survival was 4.3 years (95% CI, 3.7–5.0). SSA and familial TTR cardiomyopathy were compared; survival distribution was significantly different across groups (log-rank test = 11.97, p-value = 0.0075). We conclude that patients with SSA are primarily men who present with dominant cardiac involvement at an older age than patients with familial TTR cardiomyopathy.