We report a method for the synthesis of antimicrobial coatings on medical instruments that combines the bacteriolytic activity of lysozyme and the biocidal properties of silver nanoparticles. Colloidal suspensions of lysozyme and silver nanoparticles were electrophoretically deposited onto the surface of stainless steel surgical blades and needles. Electrodeposited films firmly adhered to stainless steel surfaces even after extensive washing and retained the hydrolytic properties of lysozyme. The antimicrobial efficacy of coatings was tested by using blades and needles in an in vitro lytic assay designed to mimic the normal application of the instruments. Coated blades and needles were used to make incisions and punctures, respectively, into agarose infused with bacterial cells. Cell lysis was seen at the contact sites, demonstrating that antimicrobial activity is transferred into the media, as well as retained on the surface of the blades and needles. Blade coatings also exhibited antimicrobial activity against a range of bacterial species. In particular, coated blades demonstrated potent bactericidal activity, reducing cell viability by at least 3 log within 1.5 h for Klebsiella pneumoniae, Bacillus anthracis Sterne, and Bacillus subtilis and within 3 h for Staphylococcus aureus and Acinetobacter baylyi. The results confirmed that complex antimicrobial coatings can be created using facile methods for silver nanoparticle synthesis and electrodeposition.