Following improvements in continuous-flow hyperpolarization technology, 129Xe has shown ever-increasing utility as a pulmonary contrast agent. However, polarization remains constrained by conflicting demands of spin-exchange efficiency and T1 relaxation during cryogenic collection. By collecting 129Xe across a range of practical conditions, we developed model to predict conditions for optimal 129Xe polarization. In many regimes, the benefits of optimal spin exchange efficiency were outweighed by polarization lost to rapid relaxation in polycrystalline 129Xe snow (T1snow = 84 minutes). For 1-L, clinical 129Xe doses, our model suggests optimal polarizations are obtained using accumulation times <30 minutes and relatively rich (2–2.3%) xenon mixtures.