Introduction: After noting inconsistent sonographic median nerve cross‐sectional area (CSA) enlargement at the wrist in very elderly patients with carpal tunnel syndrome (CTS), we systematically reviewed ultrasound, electrodiagnostic, and clinical data collected over a 12‐month period in patients from 2 age groups: 80–95 years and 40–65 years old. Methods: Clinical and electrodiagnostic CTS severity, sensitivity of ultrasound CSA (against both electrodiagnostic and clinical reference standards), and correlations between ultrasound CSA and clinical and electrodiagnostic severity were compared in both groups. Results: In very elderly patients, despite a higher prevalence of severe CTS, nerve ultrasound was less sensitive than in the younger group (54% vs. 87%, using clinical reference standard), and did not correlate with clinical (r = 0.28, P = 0.10) or electrodiagnostic (r = 0.09, P = 0.60) severity. Discussion: Median nerve ultrasound CSA at the wrist is not a sensitive marker of CTS in very elderly populations. In this work we detail and discuss potential pathophysiological underpinnings of this unexpected finding. Muscle Nerve, 2019