Acid aspiration syndrome of induction of anesthesia is a life-threatening complication whose severity is affected by both pH and volume of the aspirated gastric juice. We compared the effects of two proton pump inhibitors (PPIs), lansoprazole and omeprazole, and an H2 blocker, ranitidine, on gastric secretion in a prospective, randomized, double-blind fashion in 200 adult patients of ASA physical status I undergoing elective surgery. The patients were divided into eight groups (n = 25 each) according to their premedication. The patients received lansoprazole-lansoprazole (Group L-L), lansoprazole-placebo (Group L-P), placebo-lansoprazole (Group P-L), omeprazole-omeprazole (Group O-O), omeprazole-placebo (Group O-P), placebo-omeprazole (Group P-O), placebo-ranitidine (Group P-R), or placebo-placebo (Group P-P), as the first and second medications. The dose of the study drug was 30 mg for lansoprazole, 150 mg for ranitidine, and 80 mg for omeprazole. The first medication was administered orally at 9:00 PM on the night before surgery and the second at 5:30 AM in the morning on the day of the surgery. Each patient fasted overnight and took the drug with 20 mL of water. After tracheal intubation, gastric fluid was aspirated via an orogastric tube and the volume and pH of the aspirate were measured. The pH of the aspirated gastric fluid was higher in Groups P-R, L-L, P-L, O-O, and O-P than in Group P-P (P < 0.05). The volume of the gastric contents was similar in Groups P-0 and P-P, and the other groups had smaller gastric volume than Group P-P (P < 0.05). Gastric fluid from patients in Group P-R was the least acidic (pH 6.1 +/- 1.2) and had the least volume (0.09 +/- 0.06 mL/kg). Group L-L was comparable with Group P-R in both pH and volume, whereas Groups P-L and O-O were similar to Group P-R only in volume. The proportion of patients at risk according to the traditional criteria (pH < 2.5 and volume 0.4 mL/kg) was significantly lower in Groups L-L (0%), P-L (4%), O-O (4%), and P-R (0%) than in Group P-P (48%) (P < 0.05). We concluded that two consecutive doses of lansoprazole or a morning dose of ranitidine seemed to be the most effective preanesthetic medication for reducing gastric acidity and volume.