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Two-year, prospective cohort data from the Japan epidemiological research of occupation-related back pain study were used for this analysis.To examine the association between a new onset of low back pain (LBP) with disability and potential risk factors among initially symptom-free Japanese workers.Despite strong evidence that psychosocial issues may influence LBP onset among symptom-free persons, these and other LBP risk factors have not been well investigated in the Japanese workplace.Of 5310 participants responding to a self-administered baseline questionnaire (response rate: 86.5%), 3194 (60.2%) completed both 1- and 2-year follow-up questionnaires. The baseline questionnaire assessed individual characteristics, ergonomic work demands, and work-related psychosocial factors. The outcome of interest was new-onset LBP with disability during the follow-up period. Incidence was calculated for the participants who reported no LBP during the past year at baseline. Logistic regression was used to explore risk factors associated with new-onset LBP with disability.Of 836 participants who were symptom-free during the preceding year, 33 (3.9%) reported LBP with disability during the 2-year follow-up. In univariate analyses, “history of LBP,” “frequent lifting,” “interpersonal stress at workplace,” and “monotonous tasks” were all significant predictors of LBP incidence. All of these factors remained statistically significant or almost significant in the multivariate analysis adjusting for the other variables as well as age and sex: adjusted odds ratio (OR) and 95% confidence interval (95% CI) for history of LBP (OR: 3.25, 95% CI: 1.53–6.91), frequent lifting (OR: 3.77, 95% CI: 1.16–12.3), interpersonal stress at workplace (OR: 2.42, 95% CI: 1.08–5.43), and monotonous tasks (OR: 2.21, 95% CI: 0.99–4.94).Both ergonomic and work-related psychosocial factors may predict the development of LBP with disability among previously asymptomatic Japanese workers. Thus, workplace interventions aimed at reducing the incidence of LBP should focus on both ergonomic and psychosocial stress.