Background: Obesity increases risk of hypertension and diabetes, the leading causes of end-stage renal disease. The effect of obesity on kidney function decline in stable post-myocardial infarction patients is poorly documented. This relation was investigated in a large cohort of older post-myocardial infarction patients. Design: Data were analysed from 2410 post-myocardial infarction patients in the Alpha Omega Trial, aged 60–80 years receiving optimal pharmacotherapy treatment (79% men, 18% diabetes). Methods: Cystatin C based estimated glomerular filtration rate (eGFRcysC) was calculated at baseline and after 41 months, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Obesity was defined as body mass index ≥ 30 kg/m2 and high waist circumference as ≥102 and ≥88 cm for men and women. The relation between body mass index, waist circumference and annual eGFRcysC decline was evaluated by linear regression. Results: At baseline, mean (standard deviation) eGFRcysC was 81.5 (19.6) ml/min/1.73 m2, 23% of all patients were obese. After multivariable adjustment, the annual mean (95% confidence interval) eGFRcysC decline in men and women was –1.45 (–1.59 to –1.31) and –0.92 (–1.20 to –0.63) ml/min/1.73 m2, respectively (p = 0.001). Obese versus non-obese patients and patients with high versus normal waist circumference experienced greater annual eGFRcysC decline. Men and women showed an additional annual eGFRcysC decline of –0.35 (–0.56 to –0.14) and –0.21 (–0.55 to 0.14) ml/min/1.73 m2 per 5 kg/m2 body mass index increment (p for interaction 0.3). Conclusions: High compared to normal body mass index or waist circumference were associated with more rapid kidney function decline in older stable post-myocardial infarction patients receiving optimal drug therapy.