BACKGROUND: The hemoglobin-based oxygen carrier (HBOC-201) resuscitation fluid improves outcome in hemorrhagic shock swine models with minimal coagulopathy. Herein, coagulation parameters were evaluated after resuscitation with HBOC-201 after severe bleeding and prolonged delay to definitive care. STUDY DESIGN AND METHODS: After 55 percent estimated blood volume-controlled hemorrhage by catheter withdrawal, swine (n = 48) were resuscitated with HBOC-201 or Hextend (HEX) infused in four doses over 4 hours or not resuscitated (NON). Animals were randomly assigned in two cohorts of 4- or 24-hour simulated delay to hospital arrival (access to blood and saline infusions up to 72 hr). In vitro hematologic monitoring was assessed with complete blood count, hemostasis (thromboelastography [TEG], in vitro bleeding time [PFA]), and coagulation (prothrombin time [PT], thrombin-antithrombin, fibrinogen) indices. RESULTS: Within groups, survival was unaffected by extending delay from 4 to 24 hours. Combined survival was similar for HBOC-201 and HEX but lower for NON animals (93.5, 81.5, and 25 percent, respectively; p < 0.01). Blood transfusion requirements were lower with HBOC-201 than HEX. Elevated TEG and PFA parameters in resuscitated animals reflected fluid and blood transfusion regimens. TEG reaction time and PFA were transiently higher with HBOC-201 than with HEX during the early hospital phase. PT was increased in HEX animals. CONCLUSION: In this severe model, survival was equivalent with HBOC-201 and HEX resuscitation. HBOC-201 or HEX allowed delayed hospital arrival to 24 hours without worsening coagulation parameters, but dilutional mild coagulopathy in the hospital phase persisted with HBOC-201 due to blood transfusion avoidance. Low hematocrit suggests that blood administration after HBOC-201 resuscitation could be beneficial to replete blood cellular mass.