Background: Body mass index (BMI), the most widely used adiposity metric, cannot differentiate fat distribution from lean mass, limiting its prognostic utility. This study compared the weight-adjusted waist index (WWI) with BMI, waist-to-height ratio, and relative fat mass (RFM) as predictors of all-cause and cardiovascular mortality using a z-standard-ized framework.

Methods: Data from 18 496 adults aged ≥20 years from the National Health and Nutrition Examination Survey 2011-2018 were linked to the National Death Index through December 31, 2019. Four adiposity indices were z-standardized and analyzed using survey-weighted Cox models with sequential adjustment. Dose–response relationships were assessed using restricted cubic splines, and subgroup analyses examined the effect modification by sex, multimorbidity, and estimated glomerular filtration rate (eGFR).

Results: Over a median follow-up of 4.83 years, 976 all-cause and 291 cardiovascular deaths occurred. Weight-adjusted waist index demonstrated the strongest association with all-cause mortality (hazard ratio [HR] 1.34; 95% CI 1.23-1.46; P < .001); BMI and RFM did not reach significance. After mutual adjustment, WWI retained its association (HR 1.40; P < .001) while BMI did not reach statistical significance in the adjusted model. Weight-adjusted waist index showed a linear dose–response relationship, contrasting the J-shaped curve of BMI. The association was consistent across subgroups but attenuated in participants with eGFR < 60 (interaction P = .034).

Conclusion: Weight-adjusted waist index was the strongest independent predictor of all-cause and cardiovascular mortality among 4 adiposity indices. Its linear dose–response relationship, consistency across subgroups, and calculability from waist circumference and body weight alone support its use as a practical alternative to BMI for mortality risk stratification.