Objective This study investigates the role of age for the prospective association between physical work demands and long-term sickness absence (LTSA). Methods We followed 69 117 employees of the general working population (Work Environment and Health in Denmark study 2012-2018), without LTSA during the past 52 weeks preceding initial interview, for up to 2 years in the Danish Register for Evaluation of Marginalisation. Self-reported physical work demands were based on a combined ergonomic index including seven different types of exposure during the working day. Using weighted Cox regression analyses controlling for years of age, gender, survey year, education, lifestyle, depressive symptoms and psychosocial work factors, we determined the interaction of age with physical work demands for the risk of LTSA. Results During follow-up, 8.4% of the participants developed LTSA. Age and physical work demands interacted (p<0.01). In the fully adjusted model, very high physical work demands were associated with LTSA with HRs of 1.18 (95% CI 0.93 to 1.50), 1.57 (95% CI 1.41 to 1.75) and 2.09 (95% CI 1.81 to 2.41) for 20, 40 and 60 years old (point estimates), respectively. Results remained robust in subgroup analyses including only skilled and unskilled workers and stratified for gender. Conclusion The health consequences of high physical work demands increase with age. Workplaces should consider adapting physical work demands to the capacity of workers in different age groups.