Casting to near net shapes is a cheaper alternative manufacturing route for Ti-6Al-4V components. The large as-cast prior beta grain boundary network and its Widmanstätten morphology affects the mechanical properties of cast products. Grain refinement of this prior beta grain boundary network and its Widmanstätten morphology is critical in optimising mechanical properties. Grain refinement of the as-cast Ti-6Al-4V microstructure has been demonstrated by temporary hydrogen alloying (THP). This body of research successfully alters the Widmanstätten morphology to equiaxed morphology. However, THP does not refine the prior beta grain boundary network. The as-cast Ti-6Al-4V grain boundary network presents an indelible influence on the extent of refinement that can be achieved through THP processing. Deformation and recrystallisation is required to refine the as-cast Ti-6Al-4V prior beta grain boundary network. In a preceding study, the as-cast Ti-6Al-4V prior beta grain boundary network was successfully refined to submicron level through thermohydrogen and deformation processing (THDP). Importantly, apart from THDP processing, submicron prior beta grains in Ti-6Al-4V have only been reported in superplastic deformation (SPD) processing. The mechanism of grain refinement in SPD is well understood and attributed to the high levels of accumulated true strain (up to 8). On the contrary, it is difficult to precisely define the mechanism of microstructural modification in THDP due to the series of involved non-isothermal reactions. Understanding this refinement mechanism is important in designing processes that will provide consistent microstructure refinement. This study primarily focuses on determining the key link between hydrogen alloying, phase precipitation, grain refinement and fatigue.