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To assess the optimal moment of central vascular catheter replacement balancing infectious and mechanical complications in continuous renal replacement therapies in critically ill patients with acute renal failure.Prospective sequential trial with historical controls to compare liberal catheter replacement when clinically indicated with routine catheter replacement every 5 days in consecutive patients treated by continuous arteriovenous hemodiafiltration in a level I secondary referral intensive care unit of a university-affiliated teaching hospital. Intention-to-treat analysis.Twenty-two patients underwent catheter replacement when clinically indicated (group II), and 21 patients served as historical controls (group I). The groups were comparable for sex, age, Acute Physiology and Chronic Health Evaluation II scores, comorbidity, and creatinin and urea levels at the start of continuous arteriovenous hemodiafiltration. In group I, 71 catheters were used for 346 treatment days, and in group II, 68 catheters were used for 495 treatment days. The mean duration of catheterization was 4.9 ± 2.0 days vs. 7.3 ± 4.5 days, respectively (Student’s t-test p < .001). There was no significant difference between the incidence of colonization of catheters (46.8% in group I vs. 39.1% in group II; chi-square p = .35) In group I, bacteremia and catheter sepsis occurred in two patients, whereas this did not occur in group II. The occurrence of mechanical complications was comparable in both groups (15.5% in group I vs. 19.1% in group II). There were significantly more mechanical complications with arterial vs. venous catheters (17 vs. 7; chi-square p = .027).When catheters were changed as clinically indicated, they remained significantly longer in situ vs. being replaced routinely every 5 days; infectious and mechanical complications were comparable. The incidence of catheter sepsis was low (2.2%), and no prosthesis infection occurred. Catheter replacement when clinically indicated seems to be as safe as routine replacement every 5 days.