The effects of infusing a buffer solution on resuscitability and outcome was tested in patients during out-of-hospital cardiac arrest. A number (502) of adults with asystole or ventricular fibrillation with failure of first defibrillation attempt were entered into a prospective, randomized, double-blind, controlled trial. Of these, 245 patients received 250 ml of sodium bicarbonate-trometamol- phosphate mixture with buffering capacity 500 mmol/l and 257 patients received 250 ml 0.9% saline. Except for the investigational infusion, all patients were resuscitated according to international guidelines. Eighty-seven patients (36%) receiving buffer were admitted to hospital ICU and 24 (10%) were discharged from hospital alive, vs. 92 (36%) and 35 (14%) receiving saline (95% confidence interval (CI) for difference between groups: -6%-6% for rate of admission and -1%-9% for rate of discharge). Using a logistic regression analysis, ventricular fibrillation as initial rhythm (odds ratio 8.06, CI 3.70-17.56) improved the outcome, whereas buffer therapy had no effect (odds ratio 0.77, CI 0.43-1.41). Mean base excess at hospital admission was -9 after Tribonat vs. -11 after saline (P = 0.04, CI for difference 0.2-3.8). Only 16 of the 502 patients had arterial alkalosis on arrival in the hospital and no patient had a positive base excess. Patients resuscitated after out-of-hospital cardiac arrest had metabolic acidosis, but buffer therapy did not improve the outcome.