Rationale and Objective: Reduced kidney function is strongly associated with higher mortality but most evidence is from high-income populations. This study evaluated the relevance of kidney function to cause-specific mortality in Mexico, a country where diabetes is common and chronic kidney disease (CKD) is a major cause of morbidity and mortality. Study Design: Prospective study of 150,000 adults aged ≥35 years at recruitment (1998-2004) followed until October 2022.Setting and Participants: Participants recruited into the Mexico City Prospective Study. Analyses focused on those aged 35 to 74 years at recruitment and excluded those with prior disease (except diabetes or CKD).Exposures: Estimated glomerular filtration rate (eGFR).Outcomes: Cause-specific mortality.Analytical approach: Cox regression related eGFR to cause-specific mortality. Analyses were adjusted for socio-demographic and lifestyle factors, anthropometry, and diabetes.Results: Among 40,996 men and 85,249 women aged 35-74 years, median (IQR) eGFR was 102 (91- 110) mL/min/1.73m2 , mean (SD) BMI was 29.1 (4.9) kg/m2 , 1% had self-reported CKD, 13% had previously-diagnosed diabetes, and 12,590 died at ages 35-74 years over a median follow-up of 20.4 years. Below 105 mL/min/1.73m2 , each 15 mL/min/1.73m2 lower eGFR was associated with 32% higher all-cause mortality (RR 1.32 [95% CI 1.30-1.35]). Compared with those with an eGFR of 90- 104 mL/min/1.73m2 , those with eGFR <30 mL/min/1.73m2 had almost seven times the all-cause mortality rate (RR 6.5 [5.7-7.3]). Above 105 mL/min/1.73m2 , higher eGFR was associated with higher mortality. The strongest associations were for kidney (RR 1.75 [1.69-1.80] for each 15 mL/min/1.73m2 lower eGFR below 105 mL/min/1.73m2 ), infective (RR 1.34 [1.24-1.44]) and vascular deaths (RR 1.28 [1.24-1.33]). The absolute excess mortality risk associated with reduced eGFR was particularly high for those with diabetes.Limitations: Data on urinary albumin and non-fatal disease outcomes was unavailable.Conclusion: In Mexico, decreased kidney function is strongly associated with premature mortality, mainly from vascular, kidney, and infective causes. Prevention and management of CKD, particularly in individuals with diabetes, should be central to disease-prevention policies.