S-duct diffusers are used in aircraft with embedded engines to route ambient air to the fan face. Sizing and stealth considerations drive a need for high curvature ducts, but the curvature causes complex secondary flows that lead to total pressure distortion and swirl velocities at the engine face. These must be controlled for stable engine operation. In this paper, tubercles, a novel bio-inspired passive flow control method, are analysed numerically in a duct with transonic flow. The results are compared to experimental data obtained as part of a campaign at the Royal Military College, Canada to investigate the effects of S-duct geometry and novel passive flow control devices on the performance of transonic S-ducts. The performance of Reynolds-averaged Navier–Stokes turbulence models in the S-ducts is assessed – Menter's shear stress transport model predicts excessive losses due to the overactivity of its stress limiter. The realisable k–ɛ model gives a significant improvement in the prediction of static pressure distributions, but losses and distortion characteristics are predicted poorly due to the model's inability to resolve the effects of unsteadiness in separated regions. Large tubercle geometries are found to trigger earlier separation in the centre of the duct by concentrating low momentum fluid in valleys, but they also act as boundary layer fences away from the duct centre. Smaller geometries are found to generate vortices that re-energise the boundary layer, delaying flow separation. Methods are recommended for future computational analyses of S-ducts and new designs of tubercles.