Fault detection and protection is an important design aspect for any power converter, especially in high-power high-voltage applications, where cost of failure can be high. The three-level dc-dc converter and its varied derivatives are attractive topologies in high-voltage high-power converter applications. The protection method can not only prevent the system failure against unbalanced voltage stresses on the switches, but also provide a remedy for the system as faults occur and save the remaining components. The three-level converter is subject to voltage unbalance in certain abnormal conditions, which can result in switch overvoltage and system failure. The reasons for the unbalanced voltage stresses are fully investigated and categorized. The solutions to each abnormal condition are introduced. In addition to the voltage unbalance, the three-level converters can be protected against multiple faults by the proposed protection method through monitoring the flying capacitor voltage. Phenomena associated with each fault are thoroughly analyzed and summarized. The protection circuit is simple and can be easily implemented, while it can effectively protect the three-level converters and its derivatives, which has been verified by the experiment with a three-level parallel resonant converter.