In this work the biocompatibility of two vanadium-free Ti–Al–Nb alloys, Ti–15Al–33Nb and Ti–21Al–29Nb, was evaluated and compared to that for commercially pure titanium (CP Ti) and alumina (Al₂O₃). Fine particles were milled from sheet-processed material and implanted onto mice calvaria using an established animal model. Various stains, including methylene blue/acid fuchsin, TRAcP, and immunohistochemistry, were used on the particle-treated calvaria to measure the extent of bone deterioration of the calvaria, quantify the amount of osteoclasts, and approximate the presence of T-cells. In addition, reaction with particle-stimulated macrophages was observed and the production of the cytokine TNFα was recorded and quantified. The results indicated that the Ti–Al–Nb alloys statistically outperformed both CP Ti and Al₂O₃ in terms of their overall biocompatibility with respect to the experiments performed.