Adherence of patients with cystic fibrosis (CF) to exercise is challenging. Here we compared the physiological responses during the use of interactive video games (VG) with the cardiopulmonary exercise test (CPET) in healthy and CF subjects.Cross-sectional study including CF and healthy (CON) subjects older than 6 years. Individuals were evaluated in two visits. At visit one, anthropometric measures, spirometry and CPET were performed. In the second visit, a physical activity questionnaire was applied and gas analyses performed during the use (10 min) of both Nintendo Wii (Wii Fit Plus: (1) Obstacle Course, (2) Rhythm Boxing and (3) Free Run) and Xbox One (Just Dance 2015: (1) Love Me Again, (2) Summer and (3) Happy).Twenty-five CON and 30 CF patients were included. The mean FEV (%) was significantly lower in the CF group compared to CON. There were no differences between groups at peak exercise (CPET) for heart rate (HR), oxygen consumption (VO) and minute ventilation (V). In the CON group, games 2 and 3 (Xbox) and game 3 (Nintendo) increased HR to values similar to the anaerobic threshold (AT), while for the CF group this occurred for games 2 (Xbox) and 3 (Nintendo). As for VO and V, both groups obtained similar responses as compared to AT values in games 2 (Xbox) and 3 (Nintendo).The use of VG generated a cardiorespiratory response similar to AT levels found during CPET, indicating that it may be an alternative for exercise training of CF individuals.