Objectives: Continuous renal replacement therapy (CRRT) is the gold standard of RRT modalities in critically ill patients with severe acute kidney injury (AKI). However, there is no consensus regarding diuretic therapy when discontinuation of CRRT is attempted. We evaluated the effect of diuretics on the discontinuation of CRRT in critically ill patients from a retrospective multicenter cohort. Methods: This retrospective cohort study enrolled 1431 adult patients with acute kidney injury who survived for more than 3 days after discontinuing CRRT from the five medical centers in 2018~2020. Patients were categorized depending on the use of diuretics on the day of discontinuation of CRRT: 616 in the control (diuretics non-use) and 815 in the diuretics groups. Successful discontinuation of CRRT was defined as no renal replacement therapy requirement for 7 days after CRRT discontinuation. Results: Overall adjusted odds ratio (OR) of diuretics use for successful discontinuation of CRRT was 1.60 [95% confidence interval (CI) 1.29-1.99, P < 0.001]. Patients were stratified according to successful CRRT discontinuation scores composed of urine output, BUN, serum potassium, and mean blood pressure. Diuretics use was associated with successful discontinuation of CRRT in the intermediate score group, not in the low and high score groups [low, intermediate, and high score group: adjusted OR 1.60 (95% CI 0.79-3.23), 1.67 (1.19-2.33), and 1.10 (0.68-1.52), respectively]. Diuretics use was also associated with successful discontinuation of CRRT in oliguric patients [urine output < 200 cc/day and urine output < 400 cc/day: adjusted OR 1.59 (95% CI 1.12-2.27) and 1.91 (1.40-2.60), respectively], but not in those with urine output ≥ 400 cc/day. Conclusions: Diuretics use at CRRT discontinuation may facilitate successful discontinuation of CRRT, especially in patients with moderate probability of successful discontinuation or oliguria.