Arginine vasopressin (AVP) is a potent supplementary vasopressor in advanced vasodilatory shock, but decreases in platelet count have been reported during AVP therapy. In this study we evaluated the effects of AVP infusion on the coagulation system in advanced vasodilatory shock when compared to norepinephrine (NE) infusion alone. Forty-two patients with advanced vasodilatory shock (NE requirements >0.5 μg · kg−1 · min−1, mean arterial blood pressure <70 mm Hg) were prospectively randomized to receive an additional AVP infusion (4 U/h) or NE infusion alone. Most patients received coagulation active treatment (fresh-frozen plasma, thrombocyte concentrates, coagulation factors, and continuous venovenous hemofiltration with heparin). At baseline and 1, 24, and 48 h after randomization, coagulation laboratory variables and a modified thrombelastography were measured. There were no differences between groups in plasmatic coagulation variables. Although there was no significant difference between groups, platelet count significantly decreased in AVP patients (P = 0.036). There were no differences in results of modified thrombelastography analyses between groups. AVP infusion in advanced vasodilatory shock with severe multiorgan dysfunction syndrome does not increase plasma concentrations of Factor VIII, von Willebrand Factor antigen, and ristocetin Co-Factor but may stimulate platelet aggregation and induce thrombocytopenia. Global coagulation, assessed by modified thrombelastography, is not different from patients receiving NE infusion alone.