Background: Epidemiologic data supporting the association of accumulated inflammation from mid- to late life with late-life risk of cardiac dysfunction and heart failure (HF) is limited. Methods and Results: Among 4011 participants in the Atherosclerosis Risk in Communities study who were free of prevalent cardiovascular disease at study Visit 5, accumulated inflammation was defined as time-averaged high-sensitivity c-reactive protein (hsCRP) over 3 visits spanning 1990 to 2013. Associations with left ventricular (LV) function at Visit 5 and with incident adjudicated HF post Visit 5 were assessed using linear and Cox regression, adjusting for demographics and comorbidities. Higher accumulated hsCRP was associated with greater LV mass index, lower e’, higher E/e’, and higher adjusting for demographics (all P ≤0.01), but only with higher pulmonary artery systolic pressure after adjustment for comorbidities (P = 0.024). At 5.3 ± 1.2 year follow-up, higher accumulated hsCRP was associated with greater risk of incident HF (HR 1.31 [95% CI 1.18–1.47], P < 0.001), HFrEF (1.26 [1.05–1.52], P = 0.01), and HFpEF (1.30 [1.11–1.53], P = 0.001) in demographic-adjusted models, but not after adjustment for comorbidities (all P > 0.10). Only Visit 5 hsCRP remained associated with incident HF (1.12 [1.02–1.24], P = 0.02) after full adjustment. Conclusions: Greater accumulated inflammation is associated with worse LV function and heightened HF risk in late-life. These relationships are attenuated after adjusting for HF risk factors.