Coagulation factor XII (fXII) is a plasma serine protease which belongs to the contact activation complex responsible for initiating the intrinsic coagulation pathway. fXII deficiency is a rare congenital disorder which is not associated with an increased tendency for bleeding. However, as contact activation is impaired in fXII deficiency, both the celite- and kaolin-initiated activated clotting time (ACT) measurements are markedly prolonged, which poses a challenge for anticoagulation monitoring in patients undergoing cardiac surgery. We have successfully used the standard Hemochron® Jr. ACT+ test, which is activated by silica and phospholipid in addition to kaolin, to monitor anticoagulation for cardiopulmonary bypass in two patients with severe fXII deficiency. The ACT+ test showed low baseline values, increased adequately in response to heparin, and decreased to baseline after protamine. Importantly, there was no abnormal intra- or postoperative bleeding nor any thrombotic complications. Furthermore, in vitro dose-response ACT+ testing of fXII-deficient blood with increasing heparin concentrations supports the use of ACT+ in fXII deficiency.