Abstract Background The predictive value of estimated pulse wave velocity (ePWV) for the development of metabolic syndrome has not been extensively explored. Purpose This study aims to fill this gap by evaluating ePWV as a potential predictor for the development of metabolic syndrome in middle-aged adults. Methods Using prospective multi-center cohort database, participants aged between 40 and 69 years without metabolic syndrome at baseline were studied (enrolled from June 2001 to January 2003 and provided follow-up information spanning up to 18 years). ePWV was calculated using specific equations based on age and blood pressure. The primary outcome was the incidence of metabolic syndrome during a median follow-up period of 15.6 years (187 months). Results Of the 6,186 participants analyzed, 2,726 (44.1%) developed metabolic syndrome during the follow-up period. ePWV values were categorized into tertiles to assess their predictive value for the development of metabolic syndrome. An ePWV cut-off of 7.407 m/s was identified as a predictor of metabolic syndrome development, with a sensitivity of 0.743 and a specificity of 0.464 (Figure 1). Participants exceeding this cut-off, especially those in the third tertile (8.77–14.63 m/s), had a notably higher risk of developing metabolic syndrome. Specifically, the third tertile exhibited a 52.8% cumulative incidence compared with 30.8% in the first tertile as illustrated by Kaplan–Meier curves (Figure 2). After adjustments, participants exceeding the ePWV cut-off had a 1.425-fold increased independent risk of developing metabolic syndrome (HR, 1.425; 95% confidence interval [CI], 1.281–1.585). Furthermore, those in the third tertile showed an even higher risk with an HR of 1.530 (95% CI, 1.330–1.761) compared to first tertile, even after adjusting for multiple variables. Conclusions ePWV is a significant predictor of the development of metabolic syndrome. This finding underscores the potential of ePWV as a cardiometabolic risk assessment tool and can thus provide useful information for primary and primordial prevention strategies.Figure 1Figure 2