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Background The transition of dialysis modalities from continuous renal replacement therapy (CRRT) to intermittent hemodialysis (iHD) is frequently conducted during the recovery phase of critically ill patients with acute kidney injury. Herein, we addressed the occurrence of intradialytic hypotension (IDH) after this transition, and its association with the mortality risk. Methods A total of 541 patients with acute kidney injury who attempted to transition from CRRT to iHD at Seoul National University Hospital, Korea from 2010 to 2020 were retrospectively collected. IDH was defined as a discontinuation of dialysis because of hemodynamic instability plus a nadir systolic blood pressure <90 mm Hg or a decrease in systolic blood pressure ≥30 mm Hg during the first session of iHD. Odds ratios (ORs) of outcomes, such as in-hospital mortality and weaning from RRT, were measured using a logistic regression model after adjusting for multiple variables. Results IDH occurred in 197 patients (36%), and their mortality rate (44%) was higher than that of those without IDH (19%; OR, 2.64; 95% confidence interval [CI], 1.70–4.08). For patients exhibiting IDH, the iHD sessions delayed successful weaning from RRT (OR, 0.62; 95% CI, 0.43–0.90) compared with sessions on those without IDH. Factors such as low blood pressure, high pulse rate, low urine output, use of mechanical ventilations and vasopressors, and hypoalbuminemia were associated with IDH risk. Conclusions IDH occurrence following the transition from CRRT to iHD is associated with high mortality and delayed weaning from RRT.