Here, we report a rare case in which the inlet pressure of the oxygenator increased three times in two operations, even though two different types of oxygenators were used. A 45-year-old man underwent mitral valve repair owing to posterior cusp (P2) prolapse. Immediately after median sternotomy, the patient went into anaphylactic shock. We immediately started cardio-pulmonary bypass. The inlet pressure in company A's oxygenator increased, and the oxygenator was immediately replaced with the same type of oxygenator. However, the same occurred, and the oxygenator was exchanged for one made by company B. Thereafter, the operation was completed without further oxygenator problems.Fifty-five days after the initial surgery, a second operation was performed to repair a pseudoaneurysm at the root vent cannulation site. After induction of general anesthesia, the patient went into anaphylactic shock, as before, but circulation was maintained. Cardio-pulmonary bypass was started using company B's oxygenator, as it gave no problems at the previous surgery. However, it had to be exchanged owing to inlet pressure elevation. Thereafter, cardio-pulmonary bypass was maintained without pressure elevation, and the operation was completed. The reasons for the inlet pressure elevations are unclear.