Plasma homocysteine (tHcy) is associated with kidney disease. However, few, if any, studies have examined homocysteine in relation to arterial stiffness, with stratification by the presence or absence of early-stage chronic kidney disease (CKD). The aim of this study was to examine prospective associations between tHcy and carotid-femoral pulse wave velocity (PWV) in persons with and without early-stage CKD in a sample of community-living individuals free from end-stage renal disease, dialysis, stroke and dementia. We conducted a prospective study with 498 participants of the Maine-Syracuse Longitudinal Study (mean age 61 years). Levels of tHcy were positively related to PWV measured 4-5 years later for participants with early-stage CKD (estimated glomerular filtration rate < 60 ml min-1 per 1.73 m2). Statistical adjustment was made for multiple confounders, including demographic factors, PWV-related variables and cardiovascular risk factors (b = 4.27, 95% confidence interval: 0.23-8.31, P = 0.04). These associations were not observed in persons free from CKD. Plasma tHcy is an important predictor of arterial stiffness, as indexed by PWV, in community-living individuals with modest CKD.