Objective: Effective immobilization is crucial for the accurate delivery of radiotherapy. This study aimed to compare the effectiveness of the commonly used immobilization systems for different body regions using megavoltage CT (MVCT). Methods: Daily treatment set-up data from 212 patients treated by helical tomotherapy (Accuray, Sunnyvale, CA) in 6 body regions (52 head and neck, 41 chest, 38 abdomen, 36 pelvis, 18 breast and 27 cranium) were obtained. Based on a verification tool using the pretreatment MVCT, set-up corrections for each patient were recorded. Mean systematic and random errors of lateral, longitudinal, vertical and roll directions and threedimensional vectors were compared between immobilization systems of each region. Results: Smaller set-up deviations were observed in the Orfit system (Orfit Industries NV, Wijnegem, Belgium) of the head and neck region, while the performance of immobilization systems for the chest, abdomen and pelvis regions was similar. Larger differences were noted in the breast group, where the prone BodyFIX® system