Objective The aim of this study was to compare between arterial and venous sampling for activated clotting time ( ACT) monitoring during cardiac surgery, and to record incidence of postoperative bleeding and reopening in both the situations. Patients and methods This prospective, comparative, double-blind study was conducted on 100 patients with heart disease undergoing open heart surgery, using systemic heparinization, cardiopulmonary bypass, and protamine reversal. Patients were randomly allocated into two equal groups. In group I, arterial ACT was used as a guide for heparinization and heparin reversal. In group II, venous ACT was used as a guide for heparinization and heparin reversal. Each patient in both groups had simultaneous arterial and venous ACT carried out at the following time points: baseline, after heparinization, 10 min after heparinization, and after protamine administration. All patients were monitored for the amount of bleeding from the chest tube during the fi rst 3 h postoperatively and the incidence of reopening after surgery for the fi rst 24 h postoperatively. Results Baseline venous ACT was signifi cantly higher than arterial ACT, whereas after heparinization and after blood collection, venous ACT became signifi cantly lower. After administration of protamine, venous ACT was nonsignifi cantly lower than arterial ACT. Blood loss was signifi cantly increased in the venous group than in the arterial group. With regard to the incidence of reopening, there was an increase in the rate of reopening in the venous group than in the arterial group. Conclusion There is great individual variability between the venous and arterial ACT measures. The use of arterial samples for ACT measurement had lesser rates of postoperative bleeding and reopening.