The purpose of this clinical prospective study was to assess the effect of intramuscular injections of botulinum toxin A on energy cost of movement and walking endurance in 15 children with cerebral palsy, aged 4 to 13 years, by using incremental walking treadmill protocol to voluntary exhaustion. Oxygen-uptake response to exercise stress and endurance time were analyzed before and 2 and 6 months after botulinum toxin A injection. Endurance time was significantly improved 2 months after botulinum toxin A injection in 13 patients, and a residual improvement was still present 6 months after injection in some of them. The effect of botulinum toxin A on energy cost of movement was very variable. This study provides clinical evidence of the efficacy of botulinum toxin A in reducing the energy cost of movement and in improving the endurance of spastic muscles in children with cerebral palsy.