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Mechanically ventilated patients require appropriate settings of respiratory control variables to maintain acceptable gas exchange. To control the carbon dioxide (CO₂) level effectively and automatically, system identification based on a human subject was performed using a linear affine model and a nonlinear Hammerstein structure. Subsequently, a robust controller was designed using the H_∞ loop-shaping approach, which synthesizes the optimal controller based on a specific objective by achieving stability with guaranteed performance. For demonstration purposes, the closed-loop control ventilation system was successfully tested in a human volunteer. The experimental results indicate that the blood CO₂ level may indeed be controlled noninvasively by measuring end-tidal CO₂ from expired air. Keeping the limited amount of experimental data in mind, we conclude that H_∞ loop-shaping may be a promising technique for control of mechanical ventilation in patients with respiratory insufficiency.