Objective: The use of hypertonic sodium solutions (HSS) and lactated Ringer's (LR) solution in the resuscitation of patients with major burns was compared. Summary Background Data: Hypertonic sodium solutions have been recommended for burn resuscitation to reduce the large total volumes required with isotonic LR solution and their attendant complications. Methods: To evaluate the efficacy of this therapy in our adult burn center, we resuscitated 65 consecutive patients with HSS (290 mEq/L Na) between July 1991 and June 1993 and compared them with 109 burn patients resuscitated with LR (130 mEq/L Na) between July 1986 and June 1988 (LR-1). A subsequent 39 patients were resuscitated with LR between September 1993 and August 1994 (LR-2). Results: Patients receiving hypertonic sodium solutions versus LR 1 were similar with respect to age (46.0 vs. 43.6 years), total burn size (39.2% vs. 39.9%), incidence of inhalation injury (41.5% vs. 47.7%), and predicted mortality (34.6% vs. 30.2%). Total resuscitation volumes during the first 24 hours were lower among patients treated with HSS than those in the LR-1 group (39 ± 0.3 vs. 5.3 ± 0.2 mL/kg/%body surface area [BSA], p < 0.05). After 48 hours, however, cumulative fluid loads were similar (6.6 ± 0.6 vs. 7.5 ± 0.3 mL/kg/%BSA), and total sodium load was greater with the HSS group (1.3 ± 0.1 vs. 0.9 ± 0.1 mEq/kg/%BSA, p < 0.002). During the first 3 days after burn, serum sodium concentrations were moderately elevated in the HSS patients (153 ± 2 vs. 135 ± 1 mEq/L, p < 0001). Patients resuscitated with HSS had a fourfold increase in renal failure (40.0 vs. 10.1%, p < 0.001) and twice the mortality of LR-1 patients (53.8 vs. 26.6%, p < 0.001). In patients resuscitated with HSS, renal failure was an independent risk factor (p < 0.001, by logistic regression). Analysis of these results prompted a return to LR resuscitation (LR-2). Age (41.6 ± 2.9 years), burn size (37.8 ± 3.9 %BSA), and incidence of inhalation injury (51.3%) were similar to the earlier groups. Total sodium load was less among LR-2 patients than the HSS group (0.7 ± 0.1 mEq/kg/%BSA, p < 0.01), but similar to the LR- 1 patients. Renal failure developed in only 15.4%, and 33.3% died, similar to the LR-1 group and significantly lower than patients treated with HSS (p < 0.001 and p < 0.05, respectively). Conclusion: Hypertonic sodium solution resuscitation of burn patients did not reduce the total resuscitation volume required. Furthermore, it was associated with an increased incidence of renal failure and death. The use of HSS for burn resuscitation may be ill advised.