One of the major problems of nanofiber scaffold or other devices like cardiovascular or blood-contacting medical devices is their weak mechanical properties and the lack of hemocompatibility of their surfaces. In this study, halloysite nanotubes (HNTs) and carbon nanotubes (CNTs) were incorporated within poly(lactic-co-glycolic acid) (PLGA) nanofibers and the mechanical property and hemocompatibility of both types of composite nanofibers with different doping levels were thoroughly investigated. The morphology and internal distribution of the doped nanotubes within the nanofibers were characterized using scanning electron microscopy and transmission electron microscopy. Mechanical properties of the electrospun nanofibers were tested using a material testing machine. The hemocompatibility of the composite nanofibers was examined through hemolytic and anticoagulant assay, respectively. We show that the doped HNTs or CNTs are distributed in the nanofibers with a coaxial manner and the incorporation of HNTs or CNTs does not significantly change the morphology of the PLGA nanofibers. Importantly, the incorporation of HNTs or CNTs within PLGA nanofibers significantly improves the mechanical property of PLGA nanofibers, and PLGA nanofibers with or without doping of the HNTs and CNTs display good anticoagulant property and negligible hemolytic effect to human red blood cells. With the enhanced mechanical property, great hemocompatibility, and previously demonstrated biocompatibility of both HNTs- and CNTs-doped composite PLGA nanofibers, these composite nanofibers may be used as therapeutic artificial tissue/organ substitutes for tissue engineering applications. (c) 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013