<p>The De-Ritis ratio, also known as the aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT ratio), has been associated with poor outcomes in critically ill patients. However, data on chronic kidney disease (CKD) patients are lacking. Herein, we aimed to assess the association between De-Ritis ratio and mortality among American CKD patients. We conducted a retrospective cohort study that included 2728 individuals from the National Health and Nutrition Examination Survey (2007–2016). Participants were stratified based on the tertiles of De-Ritis ratios. The association was investigated employing the multivariate cox proportional hazard regression model. The all-cause mortality and cardiovascular disease (CVD) mortality were 24.2% (659/2728) and 5.8% (157/2728), respectively. The risk of all-cause mortality and CVD mortality increased with higher De-Ritis ratio levels in both univariate and multivariate Cox regression analyses. Compared to participants with a De-Ritis ratio ≤ 0.98, those with a De-Ritis ratio ≥ 1.32 showed a higher risk of all-cause mortality and CVD mortality in the multivariable-adjusted model [HR (95% CI), 1.50 (1.18–1.90) and 2.02 (1.17–3.50), respectively]. In the CKD population, a higher De-Ritis ratio was significantly associated with increased all-cause mortality and CVD mortality. This ratio may serve as a straightforward and cost-effective indicator for mortality in CKD patients.</p>