Aims: To determine the effect of a 16-week fitness program (strength vs. aerobic) on different indicators of body composition and components of health-related physical fitness in youths with Down syndrome. Methods and procedures outcomes: Fifty adolescents (19 girls and 31 boys; average age, 18.33 ± 1.42 years) with Down syndrome were recruited and randomized to two groups (strength group vs. aerobic group). Adolescents allocated in the aerobic group carried out a physical activity program three times a week for 16 weeks meanwhile adolescents allocated in the strength group performed a fitness program three times a week for 16 weeks. Results: The exercise group had significant improvements in all health-related physical fitness variables (p < 0.05) but not on body composition. Conclusions and implications: A sixteen week fitness program consisting of three sessions of 60 min is able to increase levels of health-related physical fitness but not on body composition in youths with Down syndrome. The aerobic program does not seem to show significant differences.