In the course of the massive penetration of alternative renewable energies, the stabilization of the electrical power network significantly relies on the off-design operation of turbines and pump-turbines in hydropower plants. The occurrence of cavitation is, however, a common phenomenon at such operating conditions, often leading to critical flow instabilities, which undercut the grid stabilizing capacity of the power plant. In order to predict and extend the stable operating range of hydraulic machines, a better understanding of the cavitating flows and mainly of the transition between stable and unstable flow regimes is required. In the case of Francis turbines operating at full load, an axisymmetric cavitating vortex rope develops at the outlet runner in the draft tube. The cavity may enter self-oscillation, with violent periodic pressure pulsations propagating throughout the entire hydraulic system. The flow fluctuations lead to dangerous electrical power swings and mechanical vibrations through a fluid-structure coupling across the runner, imposing an inconvenient and costly restriction of the operating range. The paper deals with a numerical and experimental investigation of the transition from a stable to an unstable operating point on a reduced scale model of a Francis turbine at full load. Unsteady homogeneous two-phase RANS simulations are carried out using the ANSYS CFX solver. Cavitation is modelled using the Zwart’s model that required solving an additional transport equation for the void fraction. Turbulence is solved using the SST k-ω model. Simulations are compared with the experimental measurements and some insights are provided for a first comprehensive analysis of the transition between the stable and unstable states.