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We hypothesized that the associations of urinary Cd with blood pressure and cardiovascular disease (CVD) mortality may be modified by renal function.We tested these hypotheses using data from the National Health and Nutrition Examination Survey (NHANES, 1999–2010).Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively associated with blood Cd. DBP was positively related to urinary Cd whereas SBP was inversely associated with urinary Cd. In the stratified analyses by level of eGFR, the associations between SBP and urinary Cd were not statistically significant among those with normal renal function and those with mildly reduced renal function whereas SBP significantly positively associated with urinary Cd among those with moderately or severely decreased renal function (p for trend, 0.0004). Renal function appeared to be a modifying factor of the association between urinary Cd and mortality. CVD mortality risks (p for trend, 0.04) were significantly increased with increasing urinary Cd with hazard ratios (HRs) (95% CIs) of 2.18 (0.68–7.01) for the highest quartile of urinary Cd compared to the lowest. The association between urinary Cd and CVD mortality became stronger in the stratified analyses by renal function and these associations became more consistent in those who never smoked.The inverse association between urinary Cd and blood pressure observed in previous studies may be due to lack of consideration of renal function as an effect modifier. The strength of the association between urinary Cd and CVD mortality may be underestimated without considering renal function.Renal function modifies the association between urinary Cd and blood pressure.Renal function modifies the association between urinary Cd and CVD mortality risk.The association of urinary Cd with blood pressure is present in never smokers.The association of urinary Cd with CVD mortality risk is present in never smokers.The novel findings in never smokers have very significant public health relevance.