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Reducing prolonged sitting at work has been recommended by an expert panel, but whether intermittent standing improves vascular health is unclear. We aimed to test whether using a sit–stand desk could reduce blood pressure (BP) and pulse wave velocity (PWV) during a simulated workday.Overweight/obese adults with pre-to-Stage 1 hypertension completed a randomized crossover study with two simulated workday conditions: STAND–SIT (alternating standing and sitting condition every 30 min) and SIT (continuous sitting condition). Oscillometric BP was measured hourly. Carotid–femoral, carotid–radial, and carotid–ankle PWV were measured in the morning, mid-day, and late afternoon using tonometry.Participants [n = 25, 64% male, 84% white, mean (SD) age: 42 (12) years] had average resting SBP of 132 (9) mmHg and DBP of 83 (8) mmHg. In linear mixed models, STAND–SIT resulted in a significantly lower DBP (mean ± SE: −1.0 ± 0.4 mmHg, P = 0.020) and mean arterial pressure (MAP) (−1.0 ± 0.4 mmHg, P = 0.029) compared with SIT. SBP (−0.9 ± 0.7 mmHg, P = 0.176) was not different across conditions. Carotid–ankle PWV was significantly lower during the STAND–SIT vs. SIT condition (−0.27 ± 0.13 m/s, P = 0.047), whereas carotid–femoral PWV (−0.03 ± 0.13 m/s, P = 0.831) and carotid–radial PWV (−0.30 ± 0.18 m/s, P = 0.098) were not. Changes in MAP partially explained changes in PWV.Interrupting prolonged sitting during deskwork with intermittent standing was a sufficient stimulus to slightly, but statistically significantly, decrease DBP, MAP, and carotid–ankle PWV. Though the clinical significance of the observed effects is modest, regular use of a sit–stand desk may be a practical way to lower BP and PWV while performing deskwork.