Objectives: Activated protein C (APC), an endogenous anticoagulant, has antithrombotic, fibrinolytic and anti-inflammatory properties. We recently conducted a controlled study (APCAP, activated protein C in severe acute pancreatitis) of APC treatment of patients with severe acute pancreatitis (SAP). Here we studied the effect of APC on the pivotal coagulation parameters of the surviving patients in the APCAP study. Methods: The study consisted of 20 patients of whom 10 patients had received APC and 10 patients had received placebo. Coagulation parameters, physiological anticoagulants, thrombograms and circulating levels of IL-6 and CRP were determined on admission and at days 1, 3–4 and 6–7. Results: During follow-up, the temporal levels of prothrombin time (PT) decreased and the temporal levels of thromboplastin time (TT) increased in placebo group (p < 0.001 for both), but not in APC group. The temporal levels of antithrombin (AT) increased less in APC group than in placebo group (p = 0.011). The shapes of the SAP patients’ thrombograms were strongly deranged and were marginally affected by APC treatment. Conclusions: Coagulopathy in SAP, a complex phenomenon, is not alleviated by APC treatment. Rather, the patients receiving APC are heading toward normal homeostasis of coagulation slower than patients receiving placebo.