The purpose of this study was to investigate possible effects of anti-TNF alpha therapy on cardiorespiratory fitness and physical functional capacity of patients with ankylosing spondylitis (AS). Materials and methods: Twenty-eight AS patients meeting the modified New York criteria with active disease state and an equivalent number of healthy individuals as the control were prospectively enrolled. Physical working capacity and aerobic exercise capacity of the participants were determined by using cardiopulmonary exercise tests, performed before and 4 months after initiation of anti-TNF alpha therapy. Results: The mean age of the patients was 37 ± 9.1 years, and mean duration of disease was 8.9 ± 7.6 years. Patients with AS exhibited significantly lower aerobic exercise capacity (VO2peak: 21.2 ± 5.5 vs. 27.2 ± 6.6 ml/kg/min, P = 0.001), maximum power output (110.4 ± 34.8 vs. 153 ± 39.8 W, P = 0.0001), and exercise duration (16.3 ± 2.6 vs. 19.6 ± 2.9 min, P = 0.0001) than the healthy controls. When patients were reevaluated after 4 months of anti-TNF alpha therapy, significant improvement was obtained in patients' aerobic capacity, maximum power output, and exercise duration.Conclusion: Results from this study indicate that in addition to inflammatory parameters and quality of life index, even short-term anti-TNF alpha therapy results in significant improvement in cardiopulmonary health status as objectively reflected by peak VO2, maximum work rate, and exercise duration.