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Background: Mean arterial pressure (MAP) and diastolic blood pressure (DBP) are thought to consistently decline approximately 1–3 mmHg from the aorta to peripheral large arteries, thus providing a small pressure gradient to aid blood flow. The magnitude of this gradient is important for correct waveform calibration and central BP estimation. However, there is little invasive data determining the variability in MAP and DBP from central to peripheral arteries, which was the goal of this study. Methods: 52 patients (mean age 62±11 years) undergoing cardiac angiography had intra-arterial BP measured via catheter in the ascending aorta, brachial and radial arteries by sequential pull-back. MAP was calculated by integration of ensemble averaged waveforms, and DBP from the foot of the waveforms. Results: On average, MAP and DBP decreased from the aorta-to-brachial (MAP −1.5±3.9 mmHg DBP −2.7±4.1 mmHg) and brachial-to-radial (MAP −2.0±4.4 mmHg DBP −1.8±3.3 mmHg) arteries. However, changes in aortic-to-radial MAP (range −14.9 to 6.8 mmHg) and DBP (range −13.1 to 2.1 mmHg) were highly variable, including increases in MAP among 23% of patients. Importantly, the relationship between MAP and DBP changes were synergistic, with DBP decreasing if MAP increased and vice versa. The magnitude of aorta-to-radial MAP and DBP differences were significantly related to height and age. Conclusions: Although MAP and DBP are reduced on average from central to peripheral large arteries, the magnitude of change is variable and related to patient characteristics. These new observations are highly relevant to understanding arterial hemodynamic (patho)physiology and accurate non-invasive estimates of central BP.