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Background: Millions of people are at risk from the adverse effects of arsenic exposure through drinking water. Increasingly, non-cancer effects such as cardiovascular disease have been associated with drinking water arsenic exposures. However, most studies have been conducted in highly exposed populations and lacked individual measurements. Objective: To evaluate the association between cardiovascular disease and well-water arsenic exposure. Methods: We conducted a hospital based case control study in Inner Mongolia, China. Cases and controls were prospectively identified and enrolled from a large hospital in the Hangjin Hou area. Cases were patients diagnosed with cardiovascular disease and controls were patients free from cardiovascular disease, admitted for conditions unrelated to arsenic exposure. Water from the primary water source and toenail samples were collected from each subject and tested for inorganic arsenic. Results: Arsenic exposures were moderate with mean and median arsenic exposures of 8.9 µg/L and 13.1 µg/L, respectively. A total of 298 cases and 275 controls were enrolled. The adjusted odds ratio (AOR) and corresponding 95% confidence interval (95% CI) for a 10 µg/L increase in water arsenic were 1.19 (95% CI: 1.03, 1.38). Compared to exposures less than 10 µg/L, the AOR for water arsenic exposures above 40 µg/L was 4.05 (95% CI: 1.1-14.99, p = 0.04). Nail arsenic above 1.38 µg/g was also associated with an increased risk of cardiovascular disease. Conclusions: By using standardized case definitions and collecting individual measurements of arsenic, this study addressed several limitations of previous studies. The results provide further evidence of the association between cardiovascular disease and arsenic at moderate exposures. [ABSTRACT FROM AUTHOR]