Levels of fibroblast growth factor (FGF) 23, a phosphatonin, are frequently elevated in patients with end-stage renal disease (ESRD) who are on maintenance hemodialysis (MHD). However, the role of FGF23 remains unclear because renal FGF receptor function might be impaired. The present cross-sectional study examines a cohort of patients (n = 196) on MHD who were not undergoing therapy with lipid-lowering drugs including sevelamer. Non-fasting venous blood samples were withdrawn before the hemodialysis (HD) session on the third day after the previous HD session to measure serum levels of albumin, calcium (Ca), phosphate (P), alkaline phosphatase, intact parathyroid hormone (PTH), total cholesterol (C), high-density lipoprotein (HDL)-C, low-density lipoprotein(LDL)-C, oxidative LDL-C, high-sensitivity C-reactive protein (HsCRP), interleukin-6 (IL-6), and FGF23. Nutritional status was assessed using the geriatric nutritional risk index (GNRI). Carotid intima-medial thickness (CIMT) was assessed using a B-mode ultrasound scanner. FGF23 was positively correlated with P, Ca(alb)xP product, and intact PTH, and inversely correlated with C and non-HDL-C. In the higher FGF23 tertile, levels of both non-HDL-C and C were significantly decreased and CIMT was less elevated compared to the lower FGF23 tertile. Multivariate analysis showed that the higher FGF23 tertile was independently associated with decreases in C (adjusted r(2) = 0.14) and non-HDL-C (adjusted r(2) = 0.20) levels and with a less-pronounced increase in CIMT (adjusted r(2) = 0.14). High FGF23 appears to be an independent biomarker of a decrease in C and non-HDL-C that is negatively associated with atherosclerosis in patients on MHD.