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Astronauts have complained of back pain occurring during spaceflight, presumably due to the elongation of the spine from the lack of gravity. Herniated nucleus pulposus (HNP) is known to occur in aviators exposed to high Gz and has been diagnosed in several astronauts in the immediate post–spaceflight period. It is unknown whether astronauts exposed to microgravity are at added risk for developing HNP in the post–spaceflight period due to possible in–flight intervertebral disc changes. Methods: For a preset study period, incidence rates of HNP were compared between the U.S. astronaut population and a matched control population not involved in spaceflight using the Longitudinal Study of Astronaut Health database. Using a Weibull survival model, time trends of the risk of HNP prior to and after spaceflight were compared within the astronaut group. HNP incidences in other populations that have previously been reported in the literature were also compared with results in this study. Results: The incidence of HNP was 4.3 times higher in the U.S. astronaut population (N = 321) compared to matched controls (N = 983) not involved in spaceflight. For astronauts, there was relatively more HNP in the cervical region of the spine (18 of 44) than for controls (3 of 35); however, there was no clear increase of HNP incidence in those astronauts who were high performance jet aircraft pilots. There was evidence suggesting that the risk is increased immediately after spaceflight. Conclusions: Astronauts are at higher risk of incurring HNP, especially immediately following spaceflight. [ABSTRACT FROM AUTHOR]