Elevated homocysteine (Hcy) levels have been associated with an increased risk of cognitive impairment and Alzheimer's disease (AD). Tissue factor pathway inhibitor (TFPI) has recently emerged as a candidate marker of endothelial damage in AD. We investigated the relationship between plasma levels of folate, vitamin B12, Hcy, and TFPI, as well as cognitive function in 321 [100 each with mild cognitive impairment (MCI) and AD, 121 normal subjects] Korean elderly (mean age 74.8 ± 7.2 years). Plasma folate and vitamin B12 concentrations were analyzed by radioimmunoassay, Hcy by the HPLC-fluorescence method, and TFPI by enzyme-linked immunosorbent assay. Plasma Hcy levels were higher in patients with AD and MCI than those in normal subjects (p < 0.001). The AD group had higher proportions of hyperhomocysteinemic (>15 μM) and folate deficient (<3.0 ng/mL) (p = 0.026) subjects. A multiple regression analysis after adjusting for covariates revealed positive relationships between plasma folate and the MMSE-KC and Boston Naming Test, and between plasma vitamin B12 and the Word List Memory Test in the AD group, but negative associations between plasma Hcy and the Word List Memory and Constructional Recall Tests and between plasma TFPI and the Boston Naming, Word List Recall, and Constructional Recall Tests. In contrast, only plasma folate level was positively associated with the MMSE-KC and Boston Naming Test in the MCI group. No associations were observed in the normal group. These results suggest that plasma folate, vitamin B12, Hcy, and TFPI are associated with cognitive function in cognitively impaired (AD and MCI) elderly and that the association was stronger in patients with AD.