Objectives: Physical fitness may be related to development of chronic obstructive pulmonary disease (COPD).However, long-term follow-up among healthy participants is required for minimizing bias from reverse causality.We investigated the association between objectively assessed cardiorespiratory fitness (CRF), self-reported physical activity and the very long-term risk of incident COPD.Methods: Middle-aged, employed Danish men without preexisting COPD were included in 1970-71.CRF (VO2max) was measured by bicycle ergometer test and physical activity by self-report.Risk of incident COPD was examined using multi-adjusted Cox models with time-dependent covariates.Results: Among 4730 men, 626 were diagnosed with COPD during 46 years follow-up.Risk of incident COPD was increased in low vs. moderate CFR-levels, HR 1.23 (95% CI 1.00:1.51).Risk of COPD in high CRF-levels was not significantly different from moderate CRF-levels, HR 1.03 (95% CI 0.84:1.27).High vs. low level of physical activity was associated with a reduced risk of incident COPD, HR 0.67 (95% CI 0.52:0.88).These results were unaffected by exclusion of participants who died within 10 years of inclusion.Conclusion: Low CRF increases the long-term risk of incident COPD.Higher levels of self-reported physical activity reduce the risk of incident COPD.Sensitivity analyses indicated no influence of reverse causation.