A novel biomass-mediated method to synthesize cellulose-stabilized silver nanoparticles (SNPs) and incorporate them into biocompatible/bioabsorbable poly-L-lactic acid (PLLA) for producing SNP-PLLA nanocomposite thin films was developed and the antimicrobial efficacy and biocompatibility of the SNP-PLLA films were studied. The formation and coating morphology of SNPs were characterized with UV-visible spectrophotometry and transmission electron microscopy (TEM), and the release rate of silver ion from the SNP-PLLA films was determined by inductively coupled plasma-optical emission spectrometry. Antimicrobial testing of the SNP-PLLA films performed with Staphylococcus aureus and Escherichia coli according to ISO 22196 standards demonstrated that the SNP-PLLA nanocomposite films with a SNP concentration of 700 ppm reduced colonies forming unit (CFU) counts by 99.8 and 99.99%, respectively. Despite the significant antimicrobial activity, the nanocomposite films with the same SNP concentration had little effect on the viability of human HeLa cells. This strategy that has been developed for the synthesis of nanoparticles and the formation of composite films demonstrates promise for reducing perioperative surgical site infections associated with indwelling devices. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 120: 3042-3053, 2011