Changes in intracranial pressure (ICP) during space flight have stimulated an area of research in space medicine. It is widely speculated that elevations in ICP contribute to structural and functional ocular changes, including deterioration in vision, which is also observed during space flight. The aim of this study was to investigate changes in opening pressure (OP) occurring as a result of ionizing radiation exposure (at doses and dose-rates relevant to solar particle event radiation). We used a large animal model, the Yucatan mini-pig, and were able to obtain measurements over a 90 day period. This is the first investigation to show long term recordings of ICP in a large animal model without an invasive craniotomy procedure. Further, this is the first investigation reporting increased ICP after radiation exposure. •Intracranial pressure measurements were recorded in a large animal model without an invasive craniotomy procedure.•Intracranial pressure was measured in the minipig model over an extended period of 90 days.•Solar particle event-like radiation induces increased intracranial pressure.