It is unclear whether plasma homocysteine (Hcy) has a direct noxious impact on cardiovascular (CV) system or whether its association with cardiovascular events (CVE) is mediated by established risk factors. To explore the role of Hcy in CV impairment, the study evaluated cross-sectional relationships between plasma Hcy and indices of CV organ damage together with the associations of these indices with the history of CVE.In 269 patients with a high prevalence of diabetes, dyslipidemia and hypertension were measured carotid intima-media thickness, ankle-brachial index (ABI), reactive hyperemic index, carotid-femoral pulse-wave velocity (cfPWV), left ventricular (LV) mass and cardiac index.132 patients had carotid plaque, 31 ABI<0.90, 126 endothelial dysfunction, 66 increased cfPWV, 125 LV hypertrophy (LVH), 153 decreased cardiac index and 115 history of CVE. Plasma Hcy levels were related to LV mass and ABI, after adjustment for covariates and creatinine. Significantly higher Hcy levels were found in patients with LVH (8.5[4.4] vs 7.6[2.8] μmol/L; adjusted P=0.001) and ABI<0.9 (10.4[3.8] vs 7.9[3.4] μmol/L; adjusted P=0.001), when compared to those with LV mass and ABI within limits. Hcy levels were comparable between patients with and without carotid plaques, increased arterial stiffness, impaired endothelial and LV pump function. Within markers of CV organ damage, only LVH was associated with history of CVE.This study demonstrated an independent association between Hcy and LV mass as well as between LVH and a history of CVE and suggests that LVH may represent one of the pathophysiologic links between Hcy and CV risk.