Background The prognostic value of estimated pulse wave velocity (ePWV) has been infrequently explored in high-risk patient groups. Our study aimed to evaluate the prognostic significance of ePWV among patients undergoing a percutaneous coronary intervention (PCI) with a drug-eluting stent (DES). Methods A total of 4119 consecutive subjects who underwent a PCI with a DES (mean age, 67.1 ± 11.6 years and 33.1% were female) were retrospectively analyzed. ePWV was calculated based on the patient's age and mean blood pressure. Major adverse cardiovascular events (MACE), including cardiac death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke, were evaluated. Results During a median follow-up duration of 3.51 years (interquartile range, 1.35-6.37 years), there were 746 MACEs (18.1%). A multivariable analysis showed that a higher ePWV was associated with a higher MACE incidence (middle tertile vs. the lowest tertile: hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.81-3.42; p < 0.001; the highest tertile vs. the lowest tertile: HR, 6.18; 95% CI, 4.33-8.80; p < 0.001) The inclusion of ePWV data significantly increased the global chi-square values when added to the clinical information (from 96 to 128; p < 0.001). Conclusion ePWV demonstrated a significant association with MACEs in patients who underwent DES implantation. Given its relative simplicity to calculate, ePWV could potentially serve as a valuable instrument for stratifying cardiovascular risks within this high-risk patient population.