Abstract Introduction Standing places a significant hemodynamic burden on the cardiovascular system. In healthy individuals, neurohumoral reflex mechanisms, particularly the arterial baroreflex, maintain blood pressure during standing. However, in some cases, the counterregulatory response can be excessive, resulting in a condition known as orthostatic hypertension (OrthoHT), which appears to be linked to an increased cardiovascular risk. Epidemiologically, orthostatic hypertension has been reported in 5-30% of hypertensive patients. Furthermore, in recent years, it has garnered attention as a responder group in renal denervation therapy. Purpose In hypertensive patients, sympathetic hyperactivity is expected to exacerbate cardiovascular risk. However, the relationship between OrthoHT and sympathetic nerve activity remains poorly understood. This study aims to assess the differences in sympathetic nerve activity between OrthoHT and conventional hypertensive patients using muscle sympathetic nerve activity (MSNA) measurements. Methods We conducted an examination of hypertensive patients undergoing drug treatment at our clinic between April 1, 2023, and June 30, 2023, to identify cases of OrthoHT. Only patients with essential HT were included in the HT group; patients diagnosed with secondary HT were excluded. HT patients with other active CV diseases (i.e., symptomatic cerebral/coronary artery diseases or heart failure) and/or severe renal dysfunction (estimated glomerular filtration rate <30 mL/min/1.73 m2) were also excluded. OrthoHT was defined as a sustained increase in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg within 3 minutes of standing. MSNA was recorded from the left peroneal nerve using a tungsten microelectrode at supine position. We measured MSNA in the cases for which consent was obtained. Statistical analyses were performed using SPSS software. Results Among the 183 cases, 31 were diagnosed with OrthoHT, and 7 of them consented to MSNA measurement. Of the 11 cases of hypertensive patients who consented, two groups were well age-matched. We assessed body mass index, resting systolic blood pressure, diastolic blood pressure, heart rate, blood glucose level, creatinine, cholesterol, brain natriuretic hormone, and ejection fraction measured by echocardiography, but found no significant differences between the two groups. OrthoHT patients exhibited elevated MSNA burst frequency (28.3 +/- 5.7 vs. 38.4 +/- 12.2 bursts/min, P < 0.05) and burst incidence (44.6 +/- 11.1 vs. 61.1 +/- 21.3 bursts/100 heartbeats, P < 0.05) at rest. Conclusions OrthoHT is associated with sympathetic hyperactivity compared to normal hypertensive patients, contributing to an increased cardiovascular risk.