Previous studies suggested that hypoxia and exercise may have a synergistic effect on cardiovascular and metabolic risk factors. We conducted a single blind study in overweight to obese subjects to test the hypothesis that training under hypoxia (HG, n = 24, FiO(2) = 15%) results in similar or even greater improvement in body weight and metabolic risk markers compared with exercise under normoxia (NG, n = 21, FiO(2) = 21%). After an initial metabolic evaluation including incremental exercise testing, subjects trained in normoxic or hypoxic conditions thrice weekly over a 4-week period at a heart rate corresponding to 65% of maximum oxygen uptake (VO(2max)). The experimental groups were similar at the start of the investigation and weight stable during the training period. Subjects in the hypoxia group trained at a significantly lower workload (P < 0.05). Yet, both groups showed similar improvements in VO(2max) and time to exhaustion. Respiratory quotient and lactate at the anaerobic threshold as well as body composition improved more in the hypoxia group. We conclude that in obese subjects, training in hypoxia elicits a similar or even better response in terms of physical fitness, metabolic risk markers, and body composition at a lower workload. The fact that workload and, therefore, mechanic strain can be reduced in hypoxia could be particularly beneficial in obese patients with orthopedic comorbidities.