Objectives: The aim of this study was to assess the effects of individual and work-related factors on the incidence of shoulder pain in a large French working population. Methods: A total of 3,710 workers of a French region were randomly included in a cross-sectional study between 2002 and 2005. They completed a self-administered questionnaire about musculoskeletal symptoms, individual factors and exposure to work constraints. In 2007, 2,332 responded to a follow-up questionnaire. The Nordic questionnaire was used both times to assess shoulder pain during the preceding 7 days. Associations between incident shoulder pain and individual and work-related factors at baseline were studied by multivariate logistic regression for both genders. Results: A total of 946 men and 709 women without shoulder pain at baseline were eligible for the analyses. At follow-up, 105 men (11.1%) and 145 women (20.5%) reported shoulder pain. For men, age (OR 3.3, 95% CI, 1.7–6.5 for ≥50 yr), working with arms above the shoulder (1.5; 1.0–2.3) and high perceived physical exertion (1.6; 1.0–2.5) increased the risk of incident shoulder pain. For women, the factors associated with incident shoulder pain were age (2.9; 1.5–5.8 for ≥50 yr), obesity (2.5; 1.4–4.5), temporary employment (2.1; 1.1–3.7), high perceived physical exertion (2.2; 1.4–3.5) and low decision latitude (1.6; 1.0–2.3). Conclusion: Age was the strongest predictor of incident shoulder pain in both genders. BMI and biomechanical and psychosocial factors were also identified as risk factors, whereas no factor related to work organization remained in the final models.