Objective: We conducted a prospective cohort study using 1999 to 2004 data from the National Health and Nutrition Examination Survey. A total of 6,983 patients aged over 40 years who had standardized monofilament testing for peripheral neuropathy were enrolled. Participants were divided into four groups according to the presence of CKD or PN. The hazard ratios (HRs) of all-cause mortality and cardiovascular mortality were calculated using the multivariable Cox model. Methods: During a median follow-up of 11.6 years, 2,010 participants died, including 348 of cardiovascular causes. In the multivariable Cox model adjusted for age, sex, race, education, smoking status, body mass index, hypertension, peripheral artery disease, total cholesterol and microalbuminuria, participants with both PN and CKD was significantly associated with all-cause mortality (HR, 1.62 [95% CI 1.27-2.08]; P<0.001) but not statically significant with cardiovascular mortality (HR, 1.52 [95% CI 0.94-2.47]; P=0.083) compared with those without PN and CKD. CKD participants with PN had higher risk of all-cause mortality (HR 1.63, [95% CI 1.35-1.96], P<0.001) and cardiovascular mortality (HR 1.54, [95% CI 1.09-2.16], P=0.014). Results: PN was independently increased all-cause mortality especially in CKD group. This finding suggests that close monitoring of PN in CKD patients will be needed. Conclusions: Objective: Although peripheral neuropathy (PN) is a common neurologic disease in the chronic kidney disease (CKD), studies for the association of peripheral neuropathy with mortality are lacking. Therefore, we identified the association of PN with all-cause mortality and cardiovascular (CV) mortality in the population with or without CKD. Methods: We conducted a prospective cohort study using 1999 to 2004 data from the National Health and Nutrition Examination Survey. A total of 6,983 patients aged over 40 years who had standardized monofilament testing for peripheral neuropathy were enrolled. Participants were divided into four groups according to the presence of CKD or PN. The hazard ratios (HRs) of all-cause mortality and cardiovascular mortality were calculated using the multivariable Cox model. Results: During a median follow-up of 11.6 years, 2,010 participants died, including 348 of cardiovascular causes. In the multivariable Cox model adjusted for age, sex, race, education, smoking status, body mass index, hypertension, peripheral artery disease, total cholesterol and microalbuminuria, participants with both PN and CKD was significantly associated with all-cause mortality (HR, 1.62 [95% CI 1.27-2.08]; P<0.001) but not statically significant with cardiovascular mortality (HR, 1.52 [95% CI 0.94-2.47]; P=0.083) compared with those without PN and CKD. CKD participants with PN had higher risk of all-cause mortality (HR 1.63, [95% CI 1.35-1.96], P<0.001) and cardiovascular mortality (HR 1.54, [95% CI 1.09-2.16], P=0.014). Conclusions: PN was independently increased all-cause mortality especially in CKD group. This finding suggests that close monitoring of PN in CKD patients will be needed.