Background: Over the years, environmental cadmium exposure has been linked to increased mortality. Over the years, the use of cadmium has generally decreased. Aims: Although even relatively low levels of cadmium have been associated with increased mortality in the general population, whether this applies to blood cadmium is not well understood. Methods: The authors analysed data of the National Health and Nutrition Examination Survey to study the temporal trend of cadmium exposure in the period 1988-2006 and the risk of all-cause, cancer and cardiovascular mortality associated with blood cadmium levels. Results: Urinary cadmium decreased significantly over time in males (0.58 (0.01) mcg/g to 0.41 (0.01) mcg/g; P < 0.001) but not in females (0.71 (0.09) mcg/g to 0.63 (0.08) mcg/g; P= 0.66). All-cause mortality was significantly higher in the highest quartiles compared with the lowest quartile of blood cadmium in both males (hazard ratio 1.89, 95% confidence interval 1.22, 2.89; P= 0.005) and females (hazard ratio 2.03, 95% confidence interval 1.06, 3.89; P= 0.035) after adjustment for age, race/ethnicity, smoke status, alcohol intake, annual household income and body mass index. There was also a significant association with cardiovascular mortality in females (P= 0.025). Conclusions: Our data show that elevated blood cadmium levels are associated with elevated mortality, that there seem to be gender differences in temporal trends of cadmium exposure and that blood cadmium is a proxy of chronic cadmium exposure.