We previously observed improvements in vascular endothelial function as well as exploratory measures of motor and cognitive function in a pilot study of sodium nitrite supplementation in middle‐aged and older (MA/O) adults. Here, we sought to establish the efficacy of sodium nitrite for improving endothelial function (primary outcome) while also taking advantage of the opportunity to confirm our motor and cognitive function findings in a larger randomized, placebo‐controlled, double‐blind, parallel group study with 12 weeks of sodium nitrite (80 mg/day) vs. placebo in healthy MA/O adults (n = 49, 68±1 yr) with impaired endothelial function (baseline brachial artery flow‐mediated dilation FMD <6%). Sodium nitrite increased plasma levels of nitrite acutely (10‐fold, p<0.05 vs placebo) and chronically (p<0.05) and was well‐tolerated over the 12‐week supplementation period. Vascular endothelial function, measured by brachial artery FMD, was increased by 28% vs. baseline (p<0.05) after 12 weeks of supplementation (3.9±1.2 to 5.0±1.8%, p<0.05), but unchanged with placebo (3.8±1.4 to 4.0±1.5%, p>0.05). There were no differences in secondary outcomes of motor or cognitive function assessed with measures of the NIH Toolbox and other standardized tests between the sodium nitrite and placebo group after 12 weeks (all p>0.05). There were no differences in subject characteristics, body composition or circulating markers of inflammation and oxidative stress with sodium nitrite or placebo (all p>0.05). Collectively, these results indicate that sodium nitrite supplementation for 12 weeks improves endothelial function but does not affect motor or cognitive function in healthy, high‐functioning MA/O adults. These findings suggest therapeutic strategies to enhance nitrite levels may hold promise for treating age‐related vascular endothelial dysfunction. Clinicaltrials.gov Identifier: NCT02393742 Support or Funding Information NIH R01 AG013038, K01 DK115524 and NIH/NCATS Colorado CTSA Grant Number UL1 TR002535; American Physiology Society UGREF Award This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.