The concentrations of heavy metals in both local environmental samples (water and crops) and in the whole blood of 1,152 local residents were determined by atomic absorption spectrometry. We calculated rate ratios and standardized mortality ratios based on age-, gender-, and cause-specific mortality for both the district and province. Multi-regression models were then used to evaluate the associations between the exposure to multiple heavy metals and cause-specific mortality in the studied population. Significant increases in the mean concentrations of cadmium, lead, and zinc in the blood samples were found to be associated with a substantially elevated all-cancer mortality rate in this high-exposure area (HEA). There were also significantly elevated mortality rates in the HEA for both sexes from a wide range of causes (all-cause), including cardiovascular disease (CVD), when compared with a low-exposure area (LEA). Further analysis showed positive correlations between exposure to both cadmium and lead and a higher risk of all-cancer mortality among women and for both sexes combined. In contrast, zinc exposure negatively correlated with the risk of cause-specific mortality, but this was not significant. These results of our current study thus reveal that long-term environmental exposure to both cadmium and lead is associated with an increased risk of all-cause, CVD, and all-cancer mortality, whereas zinc exposure showed a possible weak protection against death from CVD.

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