Hydrogen compression systems are essential to the production, storage, transportation, and dispensing infrastructure required for the United States energy transition. However, high operating pressures, cyclic loading, hydrogen embrittlement, seal degradation, leakage, thermal instability, and component fatigue can undermine equipment reliability, safety, and operational continuity. This study proposes an integrated reliability and operational integrity framework for hydrogen compressors combining condition monitoring, digital twins, physics-informed artificial intelligence, prognostics, and risk-based maintenance. The framework captures realtime vibration, pressure, temperature, acoustic, and leakage data to identify developing faults, estimate remaining useful life, and support timely maintenance decisions. It also links material degradation, operating severity, failure probability, and consequence assessment to improve asset prioritisation. The proposed approach is applicable to reciprocating, diaphragm, centrifugal, and electrochemical compressors deployed across hydrogen production facilities, pipeline networks, storage terminals, industrial hubs, and refuelling stations. By enabling earlier fault detection, reducing unplanned downtime, improving maintenance efficiency, and strengthening safety assurance, the framework supports dependable hydrogen infrastructure expansion and contributes to a resilient, scalable, and lower-carbon future United States energy system.