Calculating the estimated glomerular filtration rate (eGFR) using creatinine-based equations may underestimate cardiovascular risk. Cystatin C-based eGFR may be a stronger prognostic biomarker than creatinine-based eGFR when assessing cardiovascular outcomes and mortality. Our aim was to determine whether levels of serum cystatin C, as an estimator of GFR, had a higher predictive value than creatinine-based eGFR for incident cardiovascular disease among hypertensive patients. We retrospectively analyzed the records of 2016 hypertensive patients from the Hypertension Unit at Mostoles University Hospital between 2006 and 2016. We calculated the eGFR using 3 CKD-EPI equations. The outcomes we included in our study were cardiovascular death, noncardiovascular death, stroke, incident heart failure, and myocardial infarction. We used the Cox regression hazard model to estimate the hazard ratio. Our analysis found that, in terms of cardiovascular morbidity and mortality, both cystatin C-based eGFR (HR 2.88, 95% CI 1.86-4.47, P < 0.0001) showed a higher prognostic value than creatinine-based eGFR (HR 2.83, 95% CI 1.73-4.63, P < 0.0001). In terms of all-cause mortality, cystatin C-based eGFR (HR 4.24, 95% CI 2.38-7.53, P < 0.0001) showed a higher prognostic value than creatinine-based eGFR (HR 2.77, 95% CI 1.43-5.36, P < 0.0001). Our findings suggest that both cystatin C-based eGFRs may be stronger predictors of all-cause mortality and cardiovascular events in our hypertensive cohort when compared to creatinine-based eGFR, and may improve the risk assessment in certain populations.