This study aimed to analyze the factors affecting continuous renal replacement therapy (CRRT) duration in critically ill patients and provide a reference for clinical treatment. We divided patients into regional citrate anti-coagulation (RCA) and low-molecular-weight-heparin (LMWH) groups according to the anti-coagulation method and collected the relevant data, to analyze the factors associated with CRRT time. Compared with the LMWH group, the RCA group had a longer mean treatment time (55.36 ± 22.57 vs. 37.65 ± 27.09 h, p < 0.001), lower transmembrane pressure, and lower filter pressure, regardless of vascular access site. Multivariable linear regression analysis showed a significant correlation between anti-coagulation patterns, filter pressure at CRRT discontinuation, nurses' level of intensive care unit experience, pre-machine fibrinogen level, and CRRT time. Anti-coagulation is the most important factor affecting CRRT duration. Filter pressure, nurses' level of intensive care unit experience, and fibrinogen level also affecting CRRT duration.