Aims: African-American carriers of the transthyretin (TTR) valine-to-isoleucine substitution (V122I) are at increased risk of heart failure, yet many have relatively subtle abnormalities of left ventricular (LV) function. We sought to explore the influence of this mutation on left atrial (LA) structure and function in this population. Methods and results: We assessed 1225 genotyped African-Americans (age range, 67–89 years) participating in the Atherosclerosis Risk in Communities study who underwent echocardiography and were in sinus rhythm at study Visit 5 (2011 to 2013). Six LA parameters [LA maximum/minimum volume index, ejection fraction, and LA reservoir, conduit, and contractile longitudinal strains (LS)] were compared between V122I TTR variant carriers (n = 46) and non-carriers (n = 1179). LA minimum volume index was significantly greater and LA contractile LS was worse in carriers than non-carriers (19.5 ± 10.6 mL/m2 vs. 16.3 ± 8.4 mL/m2; 15.0 ± 5.8% vs. 16.8 ± 5.7%, respectively, both P < 0.05). Carriers had a significantly higher number of LA abnormalities than non-carriers (1.8 ± 2.2 vs. 1.1 ± 1.6, P = 0.009). The number of subjects with at least four LA abnormalities was significantly increased among carriers compared with non-carriers (27% vs. 12%; odds ratio 2.43; 95% confidence interval 1.06–5.58 after adjusting for age, sex, body mass index, and LV wall thickness and global LS). Conclusions: Left atrial enlargement and dysfunction were common in V122I TTR carriers with sinus rhythm than non-carriers, suggesting that abnormalities of LA function may represent early markers of subclinical disease in these individuals.