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Background: Exercise-induced arterial O 2 desaturation impacts the management of interstitial lung diseases (ILD). Recent data suggest that arterial O 2 desaturation is more severe during the 6-minute walk test (6MWT) than during the 6-minute stepper test (6MST) in ILD patients. Aims: We hypothesized that a higher ventilation (VE) during the 6MST facilitates the alveolo-arterial oxygen diffusion, minimizing O 2 desaturation. Our aim was to investigate differences in ventilator responses and gas exchange during 6MST and 6MWT. Methods: Twenty-nine patients with ILD performed a 6MWT and a 6MST in a random order. Gas exchange, heart rate (HR), and oxygen pulse saturation (SpO 2 ) were measured continuously and leg discomfort (LD) was quoted on a 10-point Borg Scale, before and at the end of each test. Results: At rest no difference in HR, VE and VO 2 was observed before both tests. As expected, the decrease in SpO 2 was significantly lower during the 6MST than during the 6MWT (-5 ± 5% vs -9 ± 7%, p 2 ) was lower (p=0.01), but VE/VO 2 and respiratory exchange ratios were higher during 6MST than during 6MWT (p vs 3 ± 2, p=0.003). Conclusion: The higher VE/VO 2 ratio may have contributed to the lower O 2 desaturation during the 6MST. The higher muscle fatigue perceived during 6MST, possibly also indicated differences of active muscle metabolism, which probably contributed to the different ventilatory responses and arterial O 2 desaturation between both tests.