KEY POINTS: A pro-inflammatory diet was associated with a higher risk of incident kidney failure. Clinical trials should assess the impact of an anti-inflammatory dietary pattern on CKD risk and progression. BACKGROUND: Diet affects inflammation and kidney health, but few studies have investigated dietary inflammatory potential in CKD progression, particularly in women. We aim to examine this association in the Women's Health Initiative. METHODS: We conducted a nonconcurrent prospective cohort study among Women's Health Initiative participants enrolled in the clinical trials and observational study (1993–1998) without baseline CKD and with available dietary intake assessments, Medicare data, and creatinine measurements at enrollment. The inflammatory potential of diets was assessed using the dietary inflammatory index, an acultural tool that quantifies diets from anti-inflammatory to proinflammatory. Scores were categorized into quartiles, with Q1 () and Q4 indicating the least and most inflammatory diets, respectively. Incident kidney failure (CKD stage G5, ESKD, or transplantation) was identified using diagnosis codes in Medicare claims from enrollment through December 31, 2019. We performed multivariable Cox proportional hazards regression and modeled death as a competing risk to determine the risk of incident kidney failure. RESULTS: Among the 17,334 women included in our study, the baseline mean age was 64.9 years (standard deviation 7.1); 33.5% self-identified as Black, 8.8% as Hispanic, 38% had hypertension, and 6.8% had diabetes mellitus. The baseline mean eGFR was 87.2 ml/min per 1.73 m. Over a mean follow-up of 11.2 years, 1852 women (10.7%) developed kidney failure. Compared with Q1, women with dietary patterns in Q4 had a 18% higher risk (95% confidence interval, 1.03 to 1.37; trend = 0.01) of developing kidney failure after adjusting for age, race and ethnicity, education, region, comorbidities, medications, smoking, energy intake, physical activity, eGFR, and body mass index. Competing risk models yielded similar results. CONCLUSIONS: A proinflammatory diet (., enriched in processed foods, refined sugars, and red meat) was associated with incident kidney failure in postmenopausal women without baseline CKD. Clinical trials are needed to assess the effect of an anti-inflammatory dietary pattern on CKD risk and progression.