In idiopathic carpal tunnel syndrome (CTS), the median nerve is enlarged within the carpal tunnel due to intraneural connective tissue proliferation. Because hypercholesterolemia, especially increase in low-density lipoprotein (LDL), has been associated with fibrogenesis, we investigated the association of median nerve cross-sectional area and prevalence of idiopathic CTS with serum lipid measurements in middle-aged patients and controls. We found that nerve area and prevalence of CTS were correlated with serum LDL levels. Thus, high LDL levels in middle age are a risk factor for idiopathic CTS, suggesting that the LDL-correlated median nerve enlargement increases the volume of the carpal tunnel contents.