OBJECTIVE This study evaluates the effect of early administration of an empirical (1 mEq/kg) sodium bicarbonate dose on survival from prehospital cardiac arrest within brief (<5 minutes), moderate (5-15 minutes), and prolonged (>15 minutes) down time. METHODS Prospective randomized, double-blinded clinical intervention trial that enrolled 874 prehospital cardiopulmonary arrest patients managed by prehospital, suburban, and rural regional emergency medical services. Over a 4-year period, the randomized experimental group received an empirical dose of bicarbonate (1 mEq/kg) after standard advanced cardiac life support interventions. Outcome was measured as survival to emergency department, as this was a prehospital study. RESULTS The overall survival rate was 13.9% (110/792) for prehospital arrest patients. There was no difference in the amount of sodium bicarbonate administered to nonsurvivors (0.859 +/- 0.284 mEq/kg) and survivors (0.8683 +/- 0.284 mEq/kg) (P = .199). Overall, there was no difference in survival in those who received bicarbonate (7.4% [58/420]), compared with those who received placebo (6.7% [52/372]) (P = .88; risk ratio, 1.0236; 0.142-0.1387). There was, however, a trend toward improved outcome with bicarbonate in prolonged (>15 minute) arrest with a 2-fold increase in survival (32.8% vs 15.4%; P = .007). CONCLUSIONS The empirical early administration of sodium bicarbonate (1 mEq/kg) has no effect on the overall outcome in prehospital cardiac arrest. However, a trend toward improvement in prolonged (>15 minutes) arrest outcome was noted.