Safe use of cardiopulmonary bypass (CPB) relies upon the ability to administer, monitor, and reverse anticoagulation. Although rare, the factor XII deficient patient creates a challenge for the perfusionist due to resultant complication in monitoring anticoagulation. There have been proposed strategies to aid in monitoring anticoagulation in the factor XII deficient patient, however documentation of successful monitoring during CPB is infrequent. With use of the Hemochron Signature Elite and ACT+ cartridges, CPB in a factor XII deficient 8-month-old was completed with predictable and reliable anticoagulation monitoring. This case report explores the current suggestions as to factor XII deficiency management with CPB.