Background: Upper extremity musculoskeletal disorders (UEMSD) are one of the most common and costly occupational health problems. We aimed to assess the population-attributable fraction (PAF) of personal and occupational risk factors associated with incident UEMSD in a working population. Methods: From 2002 to 2005, a random sample of 3710 workers from the Pays de la Loire region in France, aged 20-59 were included by occupational physicians (OPs). Between 2007 and 2010, 1611 workers were re-examined by their OPs. Subjects free from UEMSD at baseline were included in this study (1275 workers, mean age: 38.2 years). Cox regression models with equal follow-up time and robust variance estimates were used to estimate ageadjusted and multivariable-adjusted relative risks (RRs) and their 95% confidence intervals (CIs). Based on multivariable models, PAF associated with each factor included in the models was estimated. Results: During the follow-up period, 143 (11%) cases of UEMSD were diagnosed. PAFs for factors associated with the incident UEMSD risk were 30% (7 to 51) for high physical exertion (RPE Borg scale ≥12), 12% (− 0.2 to 24) for low social support, 7% (− 3 to 17) for working with arms above shoulder level (≥2 h/day), 20% (12 to 28) for age group ≥45, 13% (3 to 22) for the age group 35-44, and 12% (0.3 to 24) for female gender. Conclusions: Our study suggests that an important fraction of UEMSD can be attributed to occupational exposures after the contributions of personal and other work-related factors are considered. In terms of public health, our findings are in agreement with the ergonomic literature postulating that a high proportion of UEMSD are preventable through modifying workplace risk factors. Such information is useful to help public health practitioners and policy makers implement programs of prevention of UEMSD in the working population.