© 2016 Wiley Periodicals, Inc. Continuous Renal Replacement Therapy (CRRT) usually requires anticoagulation to prevent clotting of the extracorporeal circuit. Interruptions due to filter clotting significantly reduce total therapy time and CRRT efficacy. Although heparin has traditionally been the most common anticoagulant used for CRRT, increasing evidence suggests that heparin is less effective than regional citrate in prolonging circuit life and considerably increases patient bleeding risk. Advantages of regional citrate anticoagulation (RCA) include less bleeding, increased circuit life, and less blood transfusion requirement. RCA should be the anticoagulant of choice for CRRT.