The reactivity loss of PWR fuel with burnup has been investigated experimentally by measuring the reactivity worths of highly-burnt fuel samples in a PWR test lattice in the framework of the LWR-PROTEUS Phase II program. Seven UO2 samples cut from fuel rods irradiated in a Swiss PWR plant with burnups ranging up to ∼ 120 MWd/kg and four MOX samples with burnups up to ∼ 70 MWd/kg were inserted and withdrawn repeatedly in a test region constituted of actual PWR UO2 fuel rods in the center of the PROTEUS zero-power experimental facility. The measurements were analyzed using the CASMO-5 fuel assembly code and a cross-section library based on the ENDF/B-VII release 1 evaluation for the calculation of both the isotopic inventories of the samples and the reactivity effects in a model of the central PWR test region. The effects of nuclear data uncertainties on the calculated reactivity worths were quantified by using stochastic sampling of the data. The results show close proximity between calculated and measured reactivity effects, the overall mean of the calculated-to-experimental (C/E) ratio amounting to 0.978 with a standard deviation of 0.032. Moreover, the quality of the prediction remains at the same level throughout the very wide range of burnups of the investigated samples. The analysis thus demonstrates the high accuracy of the calculation of the reactivity of highly-burnt fuel.