Previous studies have shown large-volume resuscitation modulates coagulopathy and inflammation. Our objective was to analyze the effects of initial bolus fluids used in military and civilian settings on coagulation and inflammation in a prospective, randomized, blinded trial of resuscitation of uncontrolled hemorrhage. Fifty swine were anesthetized, intubated, and ventilated and had monitoring lines placed. A Grade V liver injury was performed followed by 30 minutes of hemorrhage. After 30 minutes, the liver was packed, and randomized fluid resuscitation was initiated during a 12-minute period with 2 L of normal saline, 2 L of lactated Ringer's solution, 250 mL of 7.5% saline with 3% Dextran, 500 mL of Hextend, or no fluid (NF). Animals were monitored for 2 hours after injury. Thrombelastograms (TEGs), prothrombin time (PT), partial thromboplastin time, fibrinogen as well as serum interleukin 6, interleukin 8, and tumor necrosis factor α levels were drawn at baseline and after 1 hour and 2 hours. The NF group had less posttreatment blood loss compared with other groups (p < 0.01). Blood loss was similar in the other groups. TEG R values in each group decreased from baseline at 1 and 2 hours (p < 0.02). The groups receiving 2 L of normal saline, 250 mL of 7.5% saline with 3% Dextran, or 500 mL of Hextend had lower TEG maximum amplitude values compared with NF group (p < 0.02). All fluids except lactated Ringer's solution resulted in significant increases in PT compared with NF, whereas all fluids resulted in significant decreases in fibrinogen compared with NF (p < 0.02). Fluid resuscitation groups as well as NF group demonstrated significant increases in inflammatory cytokines from baseline to 1 hour and baseline to 2 hours. There were no significant differences in inflammatory cytokines between groups at 2 hours. Withholding fluid resulted in the least significant change in PT, fibrinogen, and maximum amplitude and in the lowest posttreatment blood loss. Resuscitation with different initial fluid resuscitation strategies did not result in increased proinflammatory mediators compared with animals that did not receive fluid.