Serum levels of the exclusively renal-derived glycoprotein, uromodulin, a putative tubular function index, were recently associated with the development of fatal and non-fatal cardiovascular disease [CVD] outcomes during longitudinal surveillance of two cohorts undergoing diagnostic coronary angiography (Leiherer A et al. Int J Cardiol. 2017; 231:6-12; Delgado GE et al. 2017; 28: 2201-10). Using a case-cohort design (total n=685; random subcohort n=433) from the completed FAVORIT trial of chronic, stable kidney transplant recipients [KTRs], we examined the association between baseline serum uromodulin (mean ± standard deviation [SD]: 67.8 ±39.7 ng/mL), and the development of CVD (myocardial infarction, CVD death, stroke, & major revascularization procedures, pooled, n=311 events), during a median 3.7 years of follow-up. Unadjusted, weighted Cox proportional hazards modeling, based upon the subcohort uromodulin level SD (±39.7), revealed that each SD higher was associated with a 23% decreased risk for CVD (hazards ratio [HR]= 0.77; 95% confidence interval [CI]=0.65-0.92). This association was attenuated after adjustment for age, sex, smoking status, graft type, prevalent diabetes & CVD, systolic blood pressure gt140, diastolic blood pressure lt 70, estimated glomerular filtration rate [eGFR] gt=45 mL/min per 1.73m2, & natural log urinary albumin/creatinine [UACR]: (HR=0.83; 95% CI=0.67-1.04). Comparing subcohort uromodulin [ng/mL] quartile ranges (Q1=5.6-39.1; Q2=39.2-58.8; Q3=58.9-82.9; Q4=83.0-309.6), with the lowest quartile as referent, unadjusted Cox models demonstrated that the risks for CVD were as follows: Q2 v. Q1 (HR=0.92; 95% CI=0.62-1.38); Q3 v. Q1 (HR=0.69; 95% CI= 0.46-1.03); Q4 v. Q1 (HR=0.56; 95% CI=0.37-0.85). Full adjustment yielded: Q2 v. Q1 (HR=1.16; 95% CI= 0.70-1.92); Q3 v. Q1 (HR= 0.77; 95% CI=0.44-1.37); Q4 v. Q1 (HR=0.76; 95% CI=0.44-1.31). Higher serum uromodulin, an ostensible indicator of better preserved tubular function, was associated with reduced risk for the development of CVD in a large cohort of chronic, stable KTRs, but this association did not persist upon adjustment for major CVD risk factors, eGFR, & UACR.