Objectives: Continuous renal replacement therapy (CRRT) is an essential therapy for critically ill patients with acute kidney injury. Despite proper anticoagulation, CRRT circuit is frequently clotted, which causes clinical issues. In this study, we aimed to investigate the risk factors affecting the circuit lifetime. Methods: We retrospectively investigated the medical records of patients who received CRRT at a single center. The major outcome of the study was the standardized frequency of circuit exchanges during the total operating period of CRRT (eClot) and the time from CRRT initiation to first circuit clotting (tClot). We defined eClot greater than 1 as frequent circuit exchange. We collected clinical data at initial visit and before first circuit clotting respectively. Results: A total of 73 critically ill patients and 88 CRRT circuits were finally analyzed. Multiple logistic regression test indicated that femoral hemodialysis catheter (odds ratio, 4.169) was the significant risk factor for frequent circuit exchange (Table 1). Correlation test with tClot indicated that norepinephrine administration rate (r= -0.290, p= 0.007), filtration fraction of CRRT (r= -0.219, p= 0.041) were negatively correlated, while the level of HCO3- (r= 0.348, p= 0.001) and ionized calcium (r= 0.292, p= 0.029) were positively correlated. Multiple linear regression test demonstrated that HCO3- (β= 0.279, p=0.033) was the most influential risk factor for CRRT circuit lifetime (Table 2). Conclusions: This study indicates that clinical factors associated with serious patient conditions are the most important factors to predict a short CRRT circuit lifetime.