Background. The primary aim of this study was to investigate the association between BMI and musculoskeletal symptoms in interaction with physical workload. In addition, it was aimed to obtain insight into whether overweight and obesity are associated with an increase in occurrence of symptoms and/or decrease in recovery from symptoms. Methods. Based on a large working population sample (n = 44,793), using the data from The Netherlands Working Conditions Survey (NWCS), logistic regression analyses were carried out to investigate the association between BMI and musculoskeletal symptoms, with adjustment for potential confounders. Longitudinal data from the Netherlands Working Conditions Cohort Study (NWCCS) of 7,909 respondents was used for the second research aim (i.e., to investigate the transition in musculoskeletal symptoms). Results. For high BMI an increased 12-month prevalence of musculoskeletal symptoms was found (overweight: OR 1.13, 95% CI: 1.08-1.19 and obesity: OR 1.28, 95% CI: 1.19-1.39). The association was modified by physical workload, with a stronger association for employees with low physical workload than for those with high physical workload. Obesity was related to developing musculoskeletal symptoms (OR 1.37, 95% CI: 1.05-1.79) and inversely related to recovery from symptoms (OR 0.76, 95% CI: 0.59-0.97). Conclusion. BMI was associated with musculoskeletal symptoms, in particular symptoms of the lower extremity. Furthermore, the association differed for employees with high or low physical workload. Compared to employees with normal weight, obese employees had higher risk for developing symptoms as well as less recovery from symptoms. This study supports the role of biomechanical factors for the relationship between BMI and symptoms in the lower extremity.