High temperature water splitting (HTWS) via electrochemical processes are of growing interest due to their potential for achieving high thermodynamic efficiency. In particular, protonic ceramic electrolysis cells (PCECs) operating between 500°-600°C have the attractive feature that, in theory, pure dry hydrogen is produced at the hydrogen electrode (see Figure 1) and, unlike more conventional solid oxide electrochemical cells (SOECs) operating at 800°C, no further gas separation is needed. These features allow much simpler and elegant hydrogen production system concepts that have the potential to be significantly less costly and more efficient. For example, the dry H2 gas production at the fuel electrode allows for a much simpler balance-of-plant. The lower operating temperature also has numerous benefits, including lower plant heat losses, the ability to find more options for integrating various process heat sources by virtue of the lower grade heat requirements, and reduced capital cost due to a reduction in both gas process heat exchanger temperature and surface area requirements. A simple thermodynamic evaluation indicates that balance-of-plant steam generation specific energy (kJ/kg) requirements are some 17% lower when operating at 500°C versus 800°C. The present work focuses on scale-up of advancing PCEC material sets developed by collaborating faculty at the Colorado School of Mines and an industrial partner, and their design/integration into MW-scale hydrogen production systems. Realizing high efficiency HTWS systems based on novel protonic ceramics requires understanding of numerous system-level considerations. One of our efforts is largely concerned with developing viable system designs that enable >75% system efficiency at centralized hydrogen production costs of < $2/kg (without compression, dispensing, and storage). This requires evaluation of plant operating conditions, especially in the PCEC stack periphery, where operating temperature, pressure, reactant utilization, sweep gas (if any) on the fuel electrode, thermal management, gas compression, and balance-of-plant integration all play critical roles in establishing cost effective, high performance HTWS systems. In this presentation, validated PCEC models using the latest large platform experimental cell data are used to explore optimal stack design parameter selection, such as cell voltage, reactant utilization, and reactant supply composition. System design implications from parameter sensitivity studies is summarized, and a comparative techno-economic analysis of PCEC-based hydrogen production systems with SOEC and PEMEC technologies is given. Figure 1