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Background Yoga is very effective in improving health especially cardio-respiratory fitness and also overall performance in adolescents. There are no large numbers of randomized controlled studies conducted on comparing yoga with physical activity for cardio-respiratory fitness in adolescent school children with large sample size. Objective Aerobic training is known to improve physical and cardio-respiratory fitness in children. Cardio-respiratory fitness is an important indicator of health in children. In this study we evaluate the effects of yoga versus physical exercise training on cardio-respiratory fitness in adolescent school children. Subjects Eight hundred two school students from 10 schools across four districts were recruited for this study. Methods In this prospective two arm RCT around 802 students were randomized to receive daily one hour yoga training (n = 411) or physical exercise (n = 391) over a period of two months. VO2 max was estimated using 20 m shuttle run test. However, yoga (n = 377) and physical exercise (n = 371) students contributed data to the analyses. Data was analysed using students t test. Results There was a significant improvement in VO2 max using 20 m Shuttle run test in both yoga (p < 0.001) and exercise (p < 0.001) group following intervention. There was no significant change in VO2 max between yoga and physical exercise group following intervention. However, in the subgroup with an above median cut-off of VO2 max; there was a significant improvement in yoga group compared to control group following intervention (p = 0.03). Conclusion The results suggest yoga can improve cardio-respiratory fitness and aerobic capacity as physical exercise intervention in adolescent school children.