Drug-resistance infections have increased extremely quickly in the past years, emerging as a serious health problem in the world. Novel and better antimicrobial agents are still being developed to control associated microorganisms. However, this still represents a great challenge for antimicrobial agents. The aim of this study was to prepare and characterize polycaprolactone nanofibers containing silver nanoparticles and to evaluate their antimicrobial properties against various Gram-positive and negative microorganisms associated with drug resistance infections. Polycaprolactone-silver fibers (PCL-AgNPs) were prepared by reduction in situ method of Ag+ ions by N,N-dimethylformamide in tetrahydrofuran solution with the simple addition of polycaprolactone in the solution for electrospinning. The results of dynamic light scattering and UV-visible spectroscopy showed the presence of silver nanoparticles with diameters of around 10-15 nm. STEM and energy dispersive X-ray spectroscopy confirmed the presence of silver agglomerates distributed over the surface of nanofibers. All PCL-AgNPs nanofibers samples showed good and specific antibacterial effect despite low silver concentration; therefore, this activity might depend on particular microbiological and cell structure characteristics as well as concentration of silver on the nanofibers. PCL-AgNPs nanofibers might have a high potential for medical applications focused on the control of drug-resistance infections.