Hypotensive resuscitation (Hypo) has been considered an alternate resuscitation strategy in clinical settings that prevent the application of standard Advanced Trauma Life Support care. However, validation of this approach when used for prolonged periods of time remains to be demonstrated. The purpose of this study was to evaluate prolonged Hypo as an alternative to standard resuscitation using various currently available resuscitative fluids. Unanesthetized, male Sprague-Dawley rats underwent computer-controlled hemorrhagic shock and resuscitation. There were six experimental groups; nonhemorrhage (NH), nonresuscitated control (C), Hypo with lactated Ringer's (HypoLR), Hypo with Hextend, 6% hydroxyethyl starch in a balanced salt solution (HEX), Hypo with PolyHeme, a polymerized hemoglobin solution (HBOC), or standard resuscitation with LR (StandLR). Animals were bled over 15 min to a mean arterial blood pressure (MAP) of 40 mmHg where the blood pressure (BP) was held for 30 min. Hypo groups were resuscitated to 60 mmHg for 4 h followed by further resuscitation to 80 mmHg. StandLR rats were resuscitated to 80 mmHg immediately after the hemorrhage period. Animals were monitored until death or they were sacrifice at 24 h. Prolonged Hypo with HEX or LR resulted in a trend toward improved 24-h survival compared with C (71%, 65%, and 48%, respectively), and performed at least as well as StandLR (58% survival). HEX required significantly less intravenous fluid (0.7x total estimated blood volume [EBV]) compared with HypoLR (1.9x EBV) and StandLR (3.2x EBV) (P < 0.05). Although HBOC required the smallest fluid volume (0.4x EBV), survival was no better than C and it resulted in the most significant acidosis. These results support the decision to use Hextend for Hypo, a strategy currently being applied on the battlefield.