In this study, we sought to synthesize chitosan nanoparticles (CS-NPs) and characterize their morphology, efficacy in inhibiting bacterial attachment, and efficacy in eradicating bacteria established on implantable hardware. CS-NPs possess desirable properties, including antibacterial properties in biofilm-mediated infections. CS-NPs were produced using ionic gelation and characterized via scanning electron microscope imaging. Staphylococcus aureus was incubated with CS-NPs at various concentrations and compared to a 1% povidone-iodine with 1% H₂O₂ control in 24-well plates. Stainless steel bone screws were placed in six-well plates and inoculated with S. aureus. After 24 h, the screws were transferred to one of three solutions (saline, 40 mg/mL CS-NP, or 1% povidone-iodine with 1% H₂O₂). Four screws from each group were vortexed in saline and plated. The remaining screw from each group was prepped and imaged to map the location of persistent bacteria. Synthesized CS-NPs had a mean diameter of 0.39 ± 0.13 μm and circularity of 0.87 ± 0.05. The percent inhibition of bacterial attachment was 73% at 20 mg/mL, 73% at 30 mg/mL, 75% at 40 mg/mL, 79% at 50 mg/mL, and 78% at 60 mg/mL. When compared to saline, the 40 mg/mL CS-NP solution reduced bacteria on the screws by 76%. No bacteria were retrieved from the 1% povidone-iodine with 1% H₂O₂ group. This study demonstrated that CS-NP solution effectively inhibited S. aureus bacterial attachment and was more effective than saline in eradicating bacteria from orthopedic hardware, suggesting that CS-NPs have the potential for prevention and treatment of musculoskeletal infections as a component of an intraoperative surgical irrigation solution.