Background: The prevalence of low back pain (LBP) for astronauts in space (68%) is higher than the 1-mo prevalence for the general population on Earth (39%). It is unclear whether differences occur between healthy subjects and astronauts with a history of LBP. Knowledge of this issue is important to assess whether a history of LBP could have an operational impact.Methods: We evaluated LBP prospectively during short duration spaceflight (15 d; N = 20) and compared this with similar data collected during two bed rest studies (N = 40). Astronauts completed a questionnaire 5–10 d preflight, during each flight day, and 5–10 d postflight.Results: All astronauts with a history of LBP also developed LBP in flight. These astronauts reported a significantly longer duration of LBP and a different pain location. LBP was most often experienced in the central area of the lower back during spaceflight with an incidence of 70% and a mean pain level of 3 (on a scale of 0–10). Pain resolved within 10 d of flight. No neurological signs were present. The most frequently reported countermeasure was assuming a “knees to chest (fetal tuck) position” combined with stretching. Greater LBP intensity was reported in spaceflight than bed rest with a trend indicating a greater number of days of pain during spaceflight.Discussion: The current study represents a prospective study of LBP in spaceflight. The results indicate that LBP is self-limiting in spaceflight and should not pose an operational risk. Prior LBP on Earth appears to be a risk factor for LBP in spaceflight.Pool-Goudzwaard AL, Belavý DL, Hides JA, Richardson CA, Snijders CJ. Low back pain in microgravity and bed rest studies. Aerosp Med Hum Perform. 2015; 86(6):541–547.