Aim: The aim of the study was (a) to develop a three-dimensional numerical model combining the oscillation of a tapered ultrasonic file and the induced irrigant flow along with their two-way interaction in the confinement of a root canal. (b) To validate this model through comparison with experiments and theoretical (analytical) solutions of the flow. Methodology: Two partial numerical models, one for the oscillation of the ultrasonic file and another one for the irrigant flow inside the root canal around the file, were created and coupled in order to take into account the two-way coupled fluid–structure interaction. Simulations were carried out for ultrasonic K-files and for smooth wires driven at four different amplitudes in air or inside an irrigant-filled straight root canal. The oscillation pattern of the K-files was determined experimentally by Scanning Laser Vibrometry, and the flow pattern inside an artificial root canal was analysed using high-speed imaging together with Particle Image Velocimetry. Analytical solutions were obtained from an earlier study. Numerical, experimental and analytical results were compared to assess the validity of the model. Results: The comparison of the oscillation amplitude and node location of the ultrasonic files and of the irrigant flow field showed a close agreement between the simulations, experiments and theoretical solutions. Conclusions: The model is able to predict reliably the file oscillation and irrigant flow inside root canals during ultrasonic activation under similar conditions.