To examine the effects of patient and treatment variables on circuit lifespan in critically ill children requiring continuous renal replacement therapy. Retrospective observational study based on a prospective registry. Tertiary referral 30-bed PICU. One hundred sixty-one critically ill children undergoing continuous renal replacement therapy during an 8-year period (2007-2014) were included in the study. Continuous renal replacement therapy. During the study period, 161 patients received a total of 22,190 hours of continuous renal replacement therapy, with a median duration of 74.75 hours (interquartile range, 32-169.5) per patient. Of the 572 filter circuits used, 276 (48.3%) were changed due to circuit clotting and 262 (45.8%) were electively changed. Median circuit life was 24.62 hours (interquartile range, 10.6-55.3) for all filters and significantly longer for those electively removed as compared to those prematurely removed because of clotting (35.50 hr [interquartile range, 16.9-67.6] vs 22.00 hr [interquartile range, 13.8-42.5]; p < 0.001). Multivariate regression analyses revealed that admission diagnosis (p < 0.001), anticoagulation type (p < 0.001), access type (p = 0.016), and circuit size (p = 0.027) were associated with prolonged circuit life, as well as, in patients on heparin anticoagulation, with higher doses of heparin (p < 0.001) and a prolonged activated partial thromboplastin time (p < 0.001). In this study, circuit lifespan in pediatric continuous renal replacement therapy was low and appeared to depend upon the patient's diagnosis, the type of access and anticoagulation used as well as the size of the circuit used.