STUDY DESIGN. Randomized controlled trial. OBJECTIVE. Determine the effectiveness a resistive exercise countermeasure with whole-body vibration in relation to lumbo-pelvic muscle and spinal morphology changes during simulated spaceflight (bed-rest). SUMMARY OF BACKGROUND DATA. Spinal lengthening, flattening of the spinal curves, increases in disc size, and muscle atrophy are commonly seen in spaceflight simulation. This may represent a risk for low back injury. Consideration of exercise countermeasures against these changes is critical for success of long-term spaceflight missions. METHODS. Twenty healthy male subjects underwent 8-weeks of bed-rest with 6-months follow-up and were randomly allocated to an inactive control or countermeasure exercise group. Magnetic resonance imaging of the lumbo-pelvic region was conducted at regular time-points during and after bed-rest. Using uniplanar images at L4, cross-sectional areas of the multifidus, lumbar erector spinae, quadratus lumborum, psoas, anterolateral abdominal, and rectus abdominis muscles were measured. Sagittal scans were used to assess lumbar spine morphology (length, sagittal disc area and height, and intervertebral angles). RESULTS. The countermeasure group exhibited less multifidus muscle atrophy (P = 0.024) and its atrophy did not persist long-term as in the control group (up to 3-months; P < 0.006). Spinal lengthening (P = 0.03) and increases in disc area (P = 0.041) were also reduced. Significant partial correlations (P < 0.001) existed between spinal morphology and muscle cross-sectional area changes. CONCLUSION. The resistive vibration exercise countermeasure reduced, but did not entirely prevent, multifidus muscle atrophy and passive spinal tissue deconditioning during bed-rest. Atrophy of the multifidus muscles was persistent long-term in the inactive subjects. Future work could consider closer attention to spinal posture during exercise and optimizing exercise dose.