Urine epidermal growth factor (uEGF) has been found to be inversely associated with kidney function loss, whereas its associations with cardiovascular disease (CVD) and mortality have not been studied. We measured baseline uEGF levels among 2346 Systolic Blood Pressure Intervention Trial (SPRINT) participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2. A linear mixed-effects model was used to investigate the associations of uEGF with the annual eGFR change; Cox proportional hazards regression models were used to analyze its associations with the ≥30% eGFR decline, CVD, and all-cause mortality outcomes. To account for the competing risk of death, the Fine and Gray method was utilized for acute kidney injury (AKI) and end-stage kidney disease (ESKD) outcomes. At baseline, the study participants had mean age of 73 ± 9 years, mean eGFR of 46 ± 11 ml/min per 1.73 m2, and median urine albumin-to-creatinine ratio (UACR) of 15 mg/g (interquartile range: 7–49). In the multivariable-adjusted analysis including baseline urine albumin and eGFR, each 50% lower uEGF concentration was associated with 0.74% (95% confidence interval CI: 0.29–1.19) per year faster decline in eGFR and 1.17 times higher risk of ≥30% eGFR decline (95% CI: 1.00–1.36). Lower uEGF concentrations were found to be associated with increased risks of ESKD, AKI, CVD, and all-cause mortality; however, these associations did not reach statistical significance when the models were controlled for baseline urine albumin and eGFR. Among hypertensive adults with chronic kidney disease (CKD), lower baseline uEGF concentration was associated with faster eGFR decline independent of baseline albuminuria and eGFR; but not with ESKD, AKI, CVD, and all-cause mortality. Display omitted