Background: A higher slow vital capacity (VC) compared with forced vital capacity (FVC) indicates small airway collapse and air trapping. We hypothesized that a larger difference between VC and FVC (VC-FVC) would predict impaired exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Methods: Pulmonary function and incremental cardiopulmonary exercise responses were assessed in 97 COPD patients. Patients were then divided into two groups: one in which VC > FVC (n = 77) and the other in which VC <= FVC (n = 20). Results: Patients with VC > FVC had lower FEV1 and peak oxygen uptake (VO2/kg) compared with patients with VC <= FVC. There was a significant inverse correlation for the entire group between VC-FVC and peak VO2/kg (r = -0.404; p < 0.001). There was also a direct correlation between FEV1% pred and peak VO2/kg (r = 0.418; p < 0.001). The results of the multivariate regression analysis with peak VO2/kg as the dependent variable showed that VC-FVC, FEV1(% pred) and age were all significant independent predictors of peak VO2/kg. The model explained 35.9% of the peak VO2/kg variance. Conclusions: The difference between VC and FVC, easily measured by spirometry, can be used not only as an index of severity of airflow limitation, but also to predict exercise performance in COPD patients.