Plasma homocysteine associates positively with cardiovascular disease. C-to-T substitution at base 677 of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene associates with increased plasma homocysteine. The association of adiponectin with cardiovascular disease is unclear. This study of survivors of a 30-year cohort of the Jewish Israeli population, 310 men and 273 women (mean age, 70.5 ± 7.0 years for both), investigated the relationship between adiponectin and homocysteine, and between adiponectin and the MTHFR C677T genotype. Serum adiponectin associated positively with total homocysteine in both men (r = 0.27, P < .001) and women (r = 0.22, P < .001). In women, the TT MTHFR genotype associated with lower median adiponectin levels, 8.98 mg/L, compared with 9.88 and 10.57 mg/L for TC and CC, respectively (P = .05; CC vs TT, P = .01). In men, the trend was opposite, but not statistically significant: 7.90, 7.03, and 6.88 mg/L for TT, TC, and CC genotypes, respectively (P = .5). This study demonstrated a positive association between homocysteine and adiponectin in both elderly men and women and a statistically significant association between adiponectin and MTHFR C677T genotypes in women only.