BACKGROUND Leukocyte telomere length (LTL) and plasma homocysteine (HCY) have been independently associated with cardiovascular disease (CVD) morbidity and mortality. However, few studies have investigated the association between LTL and HCY levels. OBJECTIVE This study investigated the association of LTL with CVD risk factors, including HCY, in an overt CVD-free Singapore Chinese population comprised of middle aged and elderly, the age group at risk of developing CVD. METHODS The association of plasma HCY and other CVD biomarkers with LTL were assessed in 100 samples drawn from the Singapore Chinese Health Study (SCHS). SCHS, a population-based cohort, recruited Chinese individuals, aged 45-74 years, between 1993 and 1998. Questionnaire data were collected via face-to-face interviews. Known CVD biomarkers were measured from the blood collected at the time of recruitment, and LTL was measured using the conventional Southern blot method. RESULTS After adjustment for age, gender, smoking status, education, and dialect, LTL was found to be inversely associated with plasma HCY levels (p for trend=0.014). Serum urate showed a weak association (p for trend=0.056). Other CVD risk factors and nutrients, namely total cholesterol, low-density lipoprotein (LDL), triglycerides and creatinine, high-density lipoprotein (HDL), folate, and vitamin B6 showed the expected trend with LTL, but did not reach statistical significance. CONCLUSIONS LTL displayed an inverse association with plasma HCY. This LTL-HCY inverse association in subjects lacking obvious cardiovascular events suggests that telomere length may be an intermediary in the biological mechanism by which elevated HCY leads to CVD.