Objective Evidence suggests that intima–media thickness (IMT) and plasma homocysteine (Hcy) levels are associated with one another, and both appear to be related to cognitive dysfunction. However, no connection between both factors taken together and mild cognitive impairment (MCI) has been established. This study analysed potential relationships between IMT, Hcy and MCI. Methods We included 105 patients with MCI and 76 controls with no history of vascular disease. All participants underwent laboratory analyses, a carotid ultrasound, and clinical and neuropsychological assessment. We used the Mantel–Haenszel test (MHT), ANCOVA and multiple linear regression models (MLRM) to examine any associations between IMT, Hcy and cognitive state. Results The MHT revealed a significant association between IMT and risk of MCI (z = 4.285, P < 0.0001). The OR for the upper quartile vs the lower quartile was 5.12 (95% CI: 2.12–12.36). MHT also showed a clear association between Hcy levels and risk of MCI (z = 3.01, P = 0.003). OR for the upper vs the lower quartile was 3.39 (95% CI: 1.41–8.12). Additionally, we found a correlation between IMT and Hcy (r = 0.162, P = 0.032). Conclusions Our results suggest that there is a connection between IMT, Hcy levels and presence of amnestic MCI in a population with no history of clinically manifest atherosclerosis. Furthermore, there is also a connection between the IMT and Hcy levels themselves.