Introduction: Visual Impairment and Intracranial Pressure Syndrome (VIIP) has caused symptomatology during and after long duration missions on the International Space Station (ISS). Only indirect measurements of intracranial pressure (ICP), such as ultrasound, have been performed on ISS. Discussion and interest has happened at NASA about performing lumbar puncture (LP) in microgravity. Only the "blind" palpation approach and the ultrasound-assisted approach have been discussed. This article, as proof of concept, discusses the possibility of portable radiography to assist lumbar punctures in microgravity. Method: An anthropomorphic radiological phantom of an adult lumbar spine was made containing a fluid-filled space in the spinal canal with a latex membrane which simulated the dural sac and cerebrospinal fluid. A portable direct-digital radiography system with wireless transmitting image receptor and screen was used to perform image-guided lumbar puncture. Using the same equipment and technique, this procedure was then performed on a cadaver for final proof of concept. Results: Technical success was achieved in all approaches on the first try without needle redirection. There was no difference between the cadaver model and the phantom model in terms of difficulty in reaching the fluid space or visually confirming needle location. Discussion: Portable radiography via proof of concept has the potential to guide lumbar puncture while minimizing volume and mass of equipment. This could be ideal for assisting in performing lumbar puncture in microgravity, as this is the standard of care on Earth for difficult or failed "blind" lumbar punctures.