Direct hemoperfusion with polymyxin B (PMX-DHP) is an extracorporeal treatment to add to conventional therapy during unresponsive endotoxic septic shock. So far, only heparin has been used as an anticoagulant during polymyxin B therapy. We present a case report of a postsurgical septic patient treated with 2 cycles of PMX-DHP using citrate anticoagulation. Monitoring of serum calcium, postcartridge calcium, and acid-base balance was performed. The treatments were accomplished without complications. To our knowledge, this is the first published report on the use of citrate anticoagulation during PMX-DHP. We conclude that citrate anticoagulation is feasible during hemoperfusion therapy in patients with increased hemorrhagic risk.