Although total plasma homocysteine (tHcy) has been extensively studied as a risk factor of CVD, longitudinal evidence on its association with mortality is scarce, especially among the elderly. The study cohort consisted of 215 subjects (eighty-eight male and 127 female), aged 60 years or older, recruited in fourteen elderly care institutions from Asturias (Spain). All participants were free of major chronic pathology and took no vitamin and/or mineral supplements. Baseline determinations included tHcy in plasma and folate, vitamin B12 and Se in serum. Survival analyses were performed by quintiles of these factors after 6 years (mean follow-up time 4.3 years) by means of Cox regression models. During follow-up time sixty participants died. tHcy above 16.7 micromol/l was associated with an increased risk of mortality in the sample (relative risk 2.30 (95 % CI 1.02, 5.17)). Among the nutritional determinants of tHcy evaluated, folate and Se were not predictive of death risk of the cohort, while vitamin B12 showed inconsistent results. Nevertheless, mortality was significantly lower at higher serum Se levels (upper quintile), but this effect was restricted to women. Higher tHcy in both sexes and lower serum Se in women were found to be independently associated with an increased risk of death in elderly subjects.