Silica xerogel-chitosan hybrids containing vancomycin were fabricated by the sol-gel process at room temperature and their potential as a drug eluting bone replacement was evaluated in terms of their mechanical properties and drug release behaviors. Regardless of the content of chitosan, all of the prepared hybrids had a uniform mesoporous structure, which would allow the effectual loading of vancomycin. As the content of chitosan was increased, the strength, strain to failure, and work of fracture of the hybrids were significantly enhanced, while the elastic modulus was decreased. These changes in the mechanical properties were mainly attributed to the mitigation of the brittleness of the silica xerogel through its hybridization with the flexible chitosan phase. In addition, the initial burst-effect was remarkably reduced by increasing the content of chitosan. The hybrids with more than 30% chitosan could release the vancomycin for an extended period of time in a controlled manner.