Copyright © 2016 by the Shock Society. Introduction: Hypertonic crystalloid solutions, colloids, and fresh whole blood (FWB) have all been proposed for prehospital resuscitation after hemorrhage. However, there are no direct comparisons of the efficacy of these different fluids. We compared Hextend, 3% hypertonic saline (HS), and FWB in a porcine model of hemorrhagic shock. Materials and Methods: Female swine (n = 5/group) underwent splenectomy and pressure-controlled hemorrhage followed by resuscitation with Hextend, 3% HS, or FWB. They were maintained at a target mean arterial pressure (MAP) for 4 h, holding or infusing fluid as necessary. Sham animals for comparison underwent splenectomy alone. Results: The mean volume required to maintain target MAP was significantly higher for 3% HS (1,016 ± 386 mL) than for Hextend (346 ± 299 mL, P < 0.05). After 4 h of resuscitation, the MAP in the 3% HS group (44 ± 3 mmHg) was significantly lower than shams (56 ± 7 mmHg, P < 0.05). Three percent HS recipients had a significantly worse metabolic acidosis and anemia than shams or FWB recipients, as well as significant increases in serum sodium and chloride. Serum interleukin-6 was significantly elevated in 3% HS and FWB recipients relative to Hextend recipients (105.3 ± 58.6 and 97.2 ± 21 vs. 38.6 ± 27.1 pcg/mL, P < 0.05). Conclusions: HS performed inferiorly to Hextend as a volume expanding resuscitative fluid after hemorrhage. On the basis of our data, we would recommend the use of Hextend over 3% saline in far forward resuscitation after hemorrhage.