Inorganic Pyrophosphatase (IPPase) from Thermococcus thioreducens catalyzes the hydrolysis of inorganic pyrophosphate (PPi) to form orthophosphate (Pi). The action of this enzyme shifts the overall equilibrium in favor of synthesis during some ATP-dependent cellular processes. To decipher a structure-based mechanism of IPPase catalysis, X-ray and neutron crystallog. were jointly used to determine positions of important atoms, including hydrogen atoms crucial to enzyme function. High quality IPPase crystals were required. In particular, large volume crystals exceeding 1 mm3 were necessary to obtain neutron diffraction data. Even though large IPPase crystals were achievable on ground-based experiments by counter-diffusion techniques, additives such as agarose must be used to reduce convective mass transport, thus limiting crystal quality and reproducibility of exptl. results. Therefore, we designed microgravity experiments to grow large crystals of IPPase in space. IPPase was crystallized by counter-diffusion crystallization in the Granada Crystallization Facility (GCF) as a CASIS payload on board the International Space Station (ISS). In two flights, IPPase crystals with volumes greater than 6 mm3 were obtained in 2mm quartz capillaries. To-date, the largest IPPase crystals were obtained in experiments performed in the ISS. X-ray diffraction data sets were collected from Space- and Earth-grown crystals with equivalent crystal dimensions when possible. In the case where space-grown crystals had bigger volumes than those grown on the ground and thus no equivalent size Earth-grown crystals were available, the largest ground-control crystals obtainable were used for analyses. Synchrotron diffraction data sets were collected at Argonne National Lab, APS on the SBC-CAT21 BM line. X-ray diffraction data were collected with completeness near 100% across all resolution shells from crystals representing each exptl. condition. In the majority of the comparisons, space-grown crystals were superior in terms of their diffraction quality based on their reflection intensity over background as a function of resolution and mosaicity.