Background. Reduced bone mineral density (BMD), altered body composition, impaired motor performance and passive ankle dorsiflexion are side effects of acute lymphoblastic leukemia (ALL) treatment. We performed a randomized study investigating whether an exercise program could prevent these side effects. Procedure. At diagnosis we randomized 51 ALL patients (median age: 5.4 years) into a group receiving a 2-year exercise program or a control group receiving standard care. BMD of total body (BMDTB), lumbar spine (BMD LS) and body composition were measured using dual energy X-ray absorptiometry, motor performance with Bayley Scales of Infant Development or Movement-ABC, and passive ankle dorsiflexion with a goniometer. The investigator was blinded to the randomization. Results. Body fat increased equally during treatment in both groups. One year after cessation of therapy more rapid decline of excessive body fat was observed in the intervention group than in the controls (P=0.01). Lean body mass, BMDTB and BMDLS of both groups decreased equally during treatment and increased equally thereafter. Both groups showed a similar decrease in passive ankle dorsiflexion and motor performance during treatment. Adherence to the intervention program varied considerably. Adherence to intervention: 11% of children exercised daily, 37% > once a week, 16% once weekly, 36% < once a week. Conclusions. The exercise program was not more beneficial than standard care in preventing reduction in BMD, motor performance and passive ankle dorsiflexion than standard care, most likely due to unsatisfactory compliance. Increased BMI and body fat in the intervention group normalized faster after cessation of chemotherapy.