The biocompatible poly(N-vinylpyrrolidinone) (PNVP) microgels were synthesized via surfactant free emulsion polymerization with N-vinylpyrrolidinone (NVP) as the monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker at 60 degrees C. The obtained PNVP microgels are spherical in shape with hydrodynamic diameter of approximately 200 nm and narrow size distribution. The PNVP microgels show rough surfaces due to the different reaction rates of monomer NVP and cross-linker EGDMA. The obtained PNVP microgels could well disperse in phosphate-buffered saline (PBS) solution with long-term stability, which make them candidates for bioapplications. The results of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) tests indicated that the PNVP microgels are biocompatible with low toxicity even at a concentration of 1000 mu g/mL. By labeling the PNVP microgels with fluorescein comonomer, it was demonstrated that the PNVP microgels could be uptaken by human embryonic kidney 293 (HEK-293) cells. The experimental results indicated that the release of isoniazid (INH, the hydrophilic model drug) could be well described by a Fickian release, whereas the microgels exhibited burst release for 5-fluorouracil (5-fu, the hydrophobic model drug).