Estimated pulse wave velocity (ePWV) has been proposed as a potential substitute for carotid-femoral pulse wave velocity (cfPWV), serving as an indicator for assessing aortic stiffness. Arterial stiffness has emerged as a potential marker associated with adverse outcomes in various specific diseases, yet its relationship with mortality rates in the general adult population remains unstudied. This study aims to investigate the association between arterial stiffness and both all-cause and cardiovascular mortality among US adults. Data from 48,257 participants aged 20 and older in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 were analyzed. Mortality details were obtained from the National Death Index (NDI). Restricted cubic spline (RCS) functions were used to visualize the association between estimated pulse wave velocity (ePWV) and mortality risk. Weighted Cox proportional hazards models were employed to assess the independent correlation between ePWV and mortality risk. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive ability of ePWV for survival. Further subgroup analyses were performed to validate the robustness of the associations. Participants were stratified into higher (> 10.92) and lower (≤ 10.92) ePWV groups. During a median follow-up of 133.69 ± 94.42 months, 8029 (16.6%) deaths, including 2641 (5.5%) cardiovascular deaths, occurred among the 48,257 participants. The weighted Cox proportional hazards model showed that after comprehensive adjustment for covariates, individuals with higher ePWV had significantly increased risks of all-cause mortality (HR 2.67, 95% confidence interval [CI] 2.50-2.84, P < 0.001) and cardiovascular mortality (HR 2.75, 95%CI 2.46-3.07, P < 0.001). RCS regression analysis revealed a nonlinear association between ePWV, a marker of arterial stiffness, and all-cause mortality with an inflection point at 8.267 (P for nonlinear = 0.0001), while a positive linear correlation was observed with cardiovascular mortality (P for nonlinear = 0.889). This association was consistent across subgroups based on age, gender, race, body mass index, education level, marital status, smoking, alcohol consumption, diabetes, and hypertension, with significant interactions observed for all-cause mortality in the hypertension subgroup (P for interaction = 0.012) and for cardiovascular mortality in smoking (P for interaction = 0.032), diabetes (P for interaction < 0.001), and hypertension subgroups (P for interaction = 0.012). The time-dependent ROC curves indicated areas under the curve (AUCs) of 0.73, 0.80, and 0.79 for 1-year, 6-year, and 10-year survival rates, respectively, for all-cause mortality, and 0.85, 0.83, and 0.83 for cardiovascular mortality. Elevated ePWV is independently associated with increased cardiovascular mortality in US adults and exhibits a significant positive correlation with all-cause mortality in US adults beyond an ePWV threshold of 8.267.