The aim of this systematic review and meta-analysis was to assess the effect of exercise in population-based interventions to prevent low back pain (LBP) and associated disability. Comprehensive literature searches were conducted in multiple databases including PubMed, Embase, and Cochrane Library from their inception through June 2017. Thirteen randomized controlled trials and three non-randomized controlled trials qualified for meta-analyses. Exercise alone reduced the risk of LBP by 33% (risk ratio = 0.67, 95% CI: 0.53, 0.85, I2 = 23%, 8 randomized controlled trials, n = 1,634) and exercise combined with education by 27% (risk ratio = 0.73, 95% CI: 0.59, 0.91, I2 = 6%, 6 trials, n = 1,381). The severity of LBP and disability from LBP were also lower in exercise than control groups. Moreover, results were not changed by excluding the non-randomized controlled trials, or by adjustment for publication bias. Few trials assessed healthcare consultation or sick leave for LBP, and meta-analyses did not show statistically significant protective effects of exercise on those outcomes. Exercise reduces the risk of LBP and associated disability, and a combination of strengthening with either stretching or aerobic exercises performed 2–3 times/week can reasonably be recommended for prevention of LBP in the general population.Journal Abstract