Cerebral palsy (CP) is a movement disorder associated with small and weak muscles. Methods that accurately assess muscle mass in children with CP are scarce. The purpose of this study was to determine whether dual-energy X-ray absorptiometry (DXA) accurately estimates midleg muscle mass in ambulatory children with spastic CP. Ambulatory children with spastic CP and typically developing children 5-11 y were studied (n = 15/group). Fat-free soft tissue mass (FFST) and fat mass at the middle third of the tibia (i.e., midleg) were estimated using DXA. Muscle mass (muscleMRI) and muscle mass corrected for intramuscular fat (muscleMRIfc) in the midleg were estimated using magnetic resonance imaging (MRI). Statistical models were created to predict muscleMRI and muscleMRIfc using DXA. Children with CP compared to typically developing children had lower FFST (38%), muscleMRI (40%) and muscleMRIfc (47%) (all p < 0.05) and a lower ratio of muscleMRIfc to FFST (17%, p < 0.05). DXA-based models developed using data from typically developing children overestimated muscleMRI (13%) and muscleMRIfc (22%) (both p < 0.05) in children with CP. DXA-based models developed using data from children with CP explained 91% of the variance in muscleMRI and 90% of the variance in muscleMRIfc in children with CP (both p < 0.05). Moreover, the estimates were not different from muscleMRI and muscleMRIfc (both p > 0.99). We conclude that DXA-based statistical models accurately estimate midleg muscle mass in children with CP when the models are composed using data from children with CP rather than typically developing children.