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Most end-stage renal disease patients experience a reduction in blood pressure during their hemodialysis session compared to predialysis. Surprisingly, a small subset of patients will experience an unusual physiological response to dialysis that results in a paradoxical increase in blood pressure. We discuss a case that involved an exaggerated elevation in blood pressure, ultimately requiring immediate cessation of dialysis and admission to the intensive care unit for intravenous treatment of a hypertensive emergency. This case serves as a framework to introduce the infrequently discussed concept of intradialytic hypertension. The underlying pathogenesis is poorly understood with multiple theoretical etiologies including activation of the renin-angiotensin-aldosterone system, imbalances in circulating levels of endothelium-derived mediators, clearance of antihypertensive medications, increased cardiac output, and changes in arterial thickness. It is important to be cognizant of this phenomenon as emerging evidence suggests that patients with any elevation in blood pressure during hemodialysis have increased rates of both short-term and long-term mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Imburgio et al.)