Background <p>Cerebral palsy (CP) is caused by a brain lesion around birth leading to impaired motor control, bony deformities, muscle contractures, and weakness resulting in altered gait. Since the brain lesion cannot be cured, treatment aims at improving mobility. Multilevel surgery targets muscle and bony impairments but the outcome of multilevel surgery is variable and unpredictable due to our limited insight in the contribution of musculoskeletal impairments to gait alterations.</p> Methods <p>Here, we used predictive simulations based on personalized musculoskeletal models to identify the contribution of musculoskeletal impairments to altered gait in eight individuals with CP scheduled for multilevel surgery. For each individual, we generated gait patterns based on eight models with different levels of personalization. We modeled muscle weakness, muscle contractures, and/or bony deformities of hip and knee and evaluated the contribution of these impairments to deviations in kinematics by comparing simulated and experimental kinematics.</p> Results <p>The contribution of modeled musculoskeletal impairments to kinematic deficits was on average 17% and never more than 39%, in line with the limited and variable effect of multilevel surgery targeting musculoskeletal impairments. Muscle contractures had the largest effect on the predicted kinematics and their effect was magnified by bony deformities and weakness.</p> Conclusion <p>Our results suggest an important contribution of motor control and unmodeled musculoskeletal impairments (e.g. shank and foot deformities) to alterations in the gait pattern. Model-based simulations are a promising tool to determine the contribution of musculoskeletal impairments to alterations in gait kinematics in individuals with CP.</p>