In this paper, the authors present a fault diagnosis method for a Neutral Point Clamped (NPC) inverter using a Multi-layer Artificial Neural Network (MANN). The considered possible faults of NPC inverter include the open-circuit fault occurring in one single device or more devices. The upper, middle and down bridge voltages are adopted the test signals because of the difficulties in isolating some fault modes. A novel multi-layer neural network is proposed to diagnose all possible open-circuit faults. Furthermore, the Principal Component Analysis (PCA) is utilized to reduce the input size of neural network.