• Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
• The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
• Cancer Prevention and Control Program, University of South Carolina, Columbia, SC 29208, USA.

The Energy-adjusted Dietary Inflammatory Index (E-DII^TM) is a comprehensive, literature-derived index for assessing the effect of dietary constituents on inflammatory biomarkers and inflammation-related chronic diseases. Several studies have examined the association between E-DII scores and mortality, with results that vary across populations. Therefore, in the present study, we aimed to investigate the potential association between E-DII scores and all-cause, cardiovascular disease (CVD), and cancer mortality using data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial. E-DII scores, calculated based on a food-frequency questionnaire, were analyzed both as a continuous variable and after categorization into quintiles. A multivariate Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 101,832 individuals were included, with 24,141 deaths recorded after a median of 17.0 years of follow-up. In multivariable-adjusted analyses, the E-DII score was significantly associated with all-cause mortality. The HR (95% CI) in the highest E-DII quintile compared to the lowest quintile was 1.23 (1.18-1.29). The E-DII was also statistically related to CVD mortality (Q5 vs. Q1; HR, 1.30 [95% CI, 1.20-1.41]) and cancer mortality (Q5 vs. Q1; HR, 1.14 [95% CI, 1.06-1.24]). Similar results were obtained from sensitivity analyses and subgroup analyses. In conclusion, the inflammatory potential of the diet, as calculated by the E-DII, was significantly associated with overall and CVD- and cancer-specific mortality risk in the PLCO study.