Prolonged exposure to microgravity during spaceflight is thought to adversely affect the human spine because of reports that disc herniation risk is increased post-spaceflight. The increased herniation risk is highest during the first post-spaceflight year, and gradually subsides thereafter. Consequently, we hypothesized that the biomechanical properties of the intervertebral disc (IVD) deteriorate during spaceflight but then recover after acclimation to normal gravity. To test this hypothesis, we compared the compressive creep properties of caudal IVDs of murine subjects that had returned from a 13-day Shuttle mission (STS-133) to those of ground-based control mice. Spaceflight (n=6) and control (n=10) groups consisted of 13-week-old, BALB/c mice (11 weeks at launch). Mice were sacrificed +1 day, +5 days, or +7 days after the landing of STS-133. Disc height was measured in situ, and compressive creep rate was fit to a fluid transport model to determine disc biomechanical properties. Compared to controls, spaceflight mice had 12.6% lower disc height and 23.1% lower straindependence on swelling pressure. Biomechanical properties did not recover significantly over the 7-day post-flight period. Biomechanical properties of the murine caudal IVD were diminished by spaceflight, consistent with observations that prolonged exposure to microgravity increases disc herniation risk. These properties did not recover after short-term reacclimation to 1g loading.