ABSTRACT: BACKGROUND:Flexitrate, an innovative regional citrate anticoagulation (RCA) protocol, was compared to traditional RCA (tRCA) and Heparin anticoagulation protocols in intensive care patients treated with continuous renal replacement therapy (CRRT). METHODS:A single-center, retrospective, cohort study, was done in a 26-bed intensive care unit in a large community hospital. Eighty dialysis sessions (Flexitrate = 2852 h, tRCA = 3580 h and Heparin = 2026 h), performed in 53 patients, were evaluated for filter life, RCA control, and metabolic control. RESULTS:In the Flexitrate cohort, 3.8% of filters clotted, compared to 16.9% with tRCA and 28.3% with Heparin (p < 0.001 for Flexitrate compared to either tRCA or Heparin). Filter survival was significantly improved with Flexitrate compared to tRCA (HR 0.24, p = 0.018) or Heparin (HR 0.14, p = 0.004). Anticoagulation control was superior with Flexitrate with Patient Ionized Calcium out of target a median of 16% of the time, compared to 27% for tRCA (p < 0.001). Filter Ionized Calcium was out of target a median of 6.8% of the time, compared to 23% for tRCA (p = 0.03). Flexitrate produced significantly less alkalosis, hypernatremia, and hypocalcemia than tRCA, and overall metabolic control was comparable to Heparin anticoagulation. The only adverse metabolic outcome with Flexitrate was increased hypomagnesemia. CONCLUSIONS:The Flexitrate protocol extended filter life, delivered more consistent anticoagulation, and provided superior metabolic control compared to a tRCA protocol. Filter life was superior to Heparin anticoagulation, with similar metabolic control. A randomized control trial comparing these protocols is recommended.