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Background: The etiologic role of biomechanical factors for low back injury (LBI) needs to be confirmed in prospective studies that control for psychosocial factors. Methods: Complete baseline information on 1,233 vehicle operators was gathered during medical examinations and by questionnaire. First LBI during 7.5 years of follow-up was ascertained from insurance records. Hazard ratios and etiologic fractions were analyzed with Cox regression models stratified by injury severity and controlling for age, sex, height, weight, ethnicity, and biomechanical and psychosocial job factors. Severe LBI was defined as medically diagnosed postlaminectomy syndrome, spinal stenosis, herniated lumbar disc, sciatica, or spinal instability. Results: An exponential dose-response relationship was found between weekly driving hours and incidence of first LBI. Indicators of physical workload were more strongly associated with more severe low back injuries compared to less severe injuries. Rates of severe LBI increased 39% for every 10-hr increase in weekly driving (hazard ratio 1.39, 95% confidence interval 1.15-1.68). Higher risks of severe LBI were also found among operators performing heavy physical labor on cable cars (hazard ratio 2.76, 95% confidence intervals 1.24-614) or reporting more ergonomic problems at baseline HR for upper quartile 1.65 (95% confidence interval 1.08-2.50). Estimates of etiologic fractions suggest that reduction of ergonomic problems to the low level currently experienced by 25% of drivers would result in a 19% reduction of severe LBI among all drivers. A change from full- (more than 30 hr) to part-time driving (20-30 hr) could reduce the number of severe LBI by 59%, although this gain would be reduced to 28% at the company level if injuries expected among additional employees, hired to maintain full service are included. Conclusions: Duration of professional driving and ergonomic problems are independent and preventable risk factors for LBI even after adjustment for psychosocial factors. (C) 2004 Wiley-Liss, Inc.