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Abstract Blood pressure variability (BPV) and heart rate variability (HRV) have been associated with Alzheimer’s Disease and Related Dementias (ADRD) in rigorously controlled studies. However, the extent to which BPV and HRV may offer predictive information in real-world, routine clinical care is unclear. In a retrospective cohort study of 48,204 adults (age 54.9 ± 17.5 years, 60% female) receiving continuous care at a single center, we derived BPV and HRV from routinely collected clinical data. We use multivariable Cox models to evaluate the association of BPV and HRV, separately and in combination, with incident ADRD. Over a median 3 [2.4, 3.0] years, there were 443 cases of new-onset ADRD. We found that clinically derived measures of BPV, but not HRV, were consistently associated with incident ADRD. In combined analyses, only patients in both the highest quartile of BPV and lowest quartile of HRV had increased ADRD risk (HR 2.34, 95% CI 1.44–3.81). These results indicate that clinically derived BPV, rather than HRV, offers a consistent and readily available metric for ADRD risk assessment in a real-world patient care setting. Thus, implementation of BPV as a widely accessible tool could allow clinical providers to efficiently identify patients most likely to benefit from comprehensive ADRD screening.