The thalamus is a central hub of the autonomic network and thalamic volume has been associated with high-risk phenotypes for sudden cardiac death. Heart rate response to physiological stressors (e.g., standing) and the associated recovery patterns provide reliable indicators of both autonomic function and cardiovascular risk. Here we examine if thalamic volume may be a risk marker for impaired heart rate recovery in response to orthostatic challenge. The Irish Longitudinal Study on Aging involves a nationally representative sample of older individuals aged ≥50 years. Multimodal brain magnetic resonance imaging and orthostatic heart rate recovery were available for a cross-sectional sample of 430 participants. Multivariable regression and linear mixed-effects models were adjusted for head size, age, sex, education, body mass index, blood pressure, history of cardiovascular diseases and events, cardiovascular medication, diabetes mellitus, smoking, alcohol intake, timed up-and-go (a measure of physical frailty), physical exercise and depression. Smaller thalamic volume was associated with slower heart rate recovery (−1.4 bpm per 1 cm3 thalamic volume, 95% CI −2.01 to −0.82; p textless .001). In multivariable analysis, participants with smaller thalamic volumes had a mean heart rate recovery −2.7 bpm slower than participants with larger thalamic volumes (95% CI −3.89 to −1.61; p textless .001). Covariates associated with smaller thalamic volume included age, history of diabetes, and heavy alcohol consumption. Thalamic volume may be an indicator of the structural integrity of the central autonomic network. It may be a clinical biomarker for stratification of individuals at risk of autonomic dysfunction, cardiovascular events, and sudden cardiac death.