We describe a case of massive cerebral venous thrombosis following open heart surgery in a patient with a reduced level of Protein C (40% of mean level). Protein C deficiency is an inherited disorder which in the homozygous form may result in massive fatal venous thrombosis in the newborn. A Protein C level below 55% is highly suggestive of heterozygous deficiency and has been associated with a tendency to venous thrombosis although its clinical penetrance is variable. This is the first reported case of massive venous thrombosis in a patient following open heart surgery associated with Protein C deficiency.