Nanofibrous membranes, consisting of a poly(L-lactic acid) (PLLA)-silica xerogel hybrid material, were successfully fabricated from a hybrid sol using the electrospinning technique for guided bone regeneration (GBR) application. These hybrid nanofibers exhibited a homogeneous and continuous morphology, with a nano-sized dispersed silica xerogel phase in the PLLA fiber matrix. The mechanical properties, such as the tensile strength and the elastic modulus, were improved as the silica xerogel content increased up to 40%. All of the hybrid membranes exhibited highly hydrophilic surfaces and good proliferation levels. After culturing for 13 days, the cells that were cultured on the hybrid membranes exhibited a significantly higher ALP activity compared to the pure PLLA membrane. Moreover, the in vivo animal experiments that used the rat calvarial defect model revealed a remarkably improved bone regeneration ability for the hybrid membrane compared to pure PLLA. These results demonstrated the feasibility of these hybrid membranes for efficient GBR. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 100B: 321–330, 2012.