Background: Despite abundant literature, the treatment of iliotibial band syndrome (ITBS) in cyclists remains complicated as it lacks evidence-based recommendations. Purpose: The aim of this study was to develop a musculoskeletal modelling approach that investigates three potential biomechanical determinants of ITBS (strain, strain rate and compression force) and to use this approach to investigate the effect of saddle setback. Design: Cross-sectional Methods: An existing 3D lower-body musculoskeletal model was adapted to cycling and to the computation of three putative pathomechanisms responsible for ITBS: ITB strain, ITB strain rate, and compression force between ITB and the lateral femoral epicondyle (LFE). Lower limb kinematics recorded from ten welltrained healthy cyclists served as input data of the model. Cyclists pedalled at a steady state (90rpm and 200W) on an ergometer, and three different saddle setback conditions were tested. The theoretical combined influence of hip and knee joint angles on ITBS was investigated and analysed through the lens of individual pedalling technique. Results: ITB-LFE compression force was the only parameter significantly affected by saddle setback and supports the hypothesis that compression force is likely to be a determinant factor in ITBS etiology. Furthermore, results showed that ITB-LFE compression force increases in individuals whose pedalling technique exacerbates hip extension-adduction and/or knee extension-internal rotation. Conclusion: This approach has the potential to be advantageously implemented as an additional tool to help diagnose/correct potentially harmful sport techniques and optimize equipment setup/design.