A single determination of EGFR associates with subsequent mortality risk. Prior decline in EGFR indicates loss of kidney function, but the relationship tomortality risk is uncertain. We conducted an individual-level meta-analysis of the risk ofmortality associatedwith antecedent EGFR slope, adjusting for established risk factors, including last EGFR, among 1.2million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an EGFR slope,25ml/min per 1.73 m2 per year, whereas 7%and 4% had a slope .5 ml/min per 1.73 m2 per year, respectively. Compared with a slope of 0 ml/min per 1.73 m2 per year, a slope of 26 ml/min per 1.73 m2 per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m2 per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus ,3 years). We conclude that prior decline or rise in EGFR associates with an increased risk of mortality, independent of current EGFR.