The most frequent causes of anaphylaxis during anesthesia are neuromuscular blocking agents, antibiotics, and latex. Proton pump inhibitors (PPI) are widely used during major surgery for the prevention of stress ulcers, but cases of perioperative anaphylactic reactions to these have rarely been reported. We present a 50-year-old male patient who experienced an episode of anaphylaxis with hypoxemia, hypotension, tachycardia, and generalized erythema after intravenous injection of pantoprazole 40 mg and methylprednisolone 1 g during general anesthesia. After resuscitation, the patient recovered without any sequelae. Six months after the surgery, a skin test was positive to pantoprazole.