Tritium clean-up systems typically deploy gas processing technologies between stages of palladium-silver (Pd/Ag) diffusers/permeators. The number of diffusers positioned before and after a gas clean-up process to obtain optimal system performance will vary with feed gas inert composition. A simple method to analyze optimal diffuser configuration is presented. The method assumes equilibrium across the Pd/Ag tubes and system flows are limited by diffuser vacuum pump speeds preceding or following the clean-up process. A plot of system feed as a function of inert feed gas composition for various diffuser configuration allows selection of a diffuser configuration for maximum throughput based on feed gas composition.