We explored the role of vancomycin-supplemented cancellous bone allografts in hip revision surgery. We evaluated the incorporation of these allografts in 18 pigs' radiographs, histology, and immunohistochemistry. High-quality radiographs, histologic examination, and immunologic expression of metalloproteinase-13 and transforming growth factor-beta 2 indicated vancomycin did not considerably affect bone graft incorporation. Elution, bioactivity, and nephrotoxicity were subsequently tested in 20 patients who underwent hip reconstruction with this method. Local active bactericidal levels of vancomycin reached 1400.5 microg/mL (average 5-point level, 367.19 microg/mL). Vancomycin was present in urine until day 15 without any sign of nephrotoxicity. Clinical analysis was performed in 30 patients whose hips underwent reconstruction with vancomycin-supplemented cancellous bone allograft. At a minimum 2-year followup, infection control was attained in 29 of 30 patients (reinfection rate, 3.3%; 95% confidence interval, 0.08-17%) without evidence of graft resorption. Histologic observations performed in two patients whose hips were reconstructed with this technique were similar to the ones reported in nonsupplemented bone allografts. Our findings encourage the continued use of vancomycin-supplemented bone allografts in reconstructive orthopaedic surgery.