Antibiotic resistance has prompted the search for new agents that can inhibit bacterial growth. Moreover, colonization of abiotic surfaces by microorganisms and the formation of biofilms is a major cause of infections associated with medical implants, resulting in prolonged hospitalization periods and patient mortality. In this study we describe a water-based synthesis of yttrium fluoride (YF₃) nanoparticles (NPs) using sonochemistry. The sonochemical irradiation of an aqueous solution of yttrium (III) acetate tetrahydrate [Y(Ac)₃ · (H₂O)₄], containing acidic HF as the fluorine ion source, yielded nanocrystalline needle-shaped YF₃ particles. The obtained NPs were characterized by scanning electron microscopy and X-ray elemental analysis. NP crystallinity was confirmed by electron and powder X-ray diffractions. YF₃ NPs showed antibacterial properties against two common bacterial pathogens (Escherichia coli and Staphylococcus aureus) at a μg/mL range. We were also able to demonstrate that antimicrobial activity was dependent on NP size. In addition, catheters were surface modified with YF₃ NPs using a one-step synthesis and coating process. The coating procedure yielded a homogeneous YF₃ NP layer on the catheter, as analyzed by scanning electron microscopy and energy dispersive spectroscopy. These YF₃ NP-modified catheters were investigated for their ability to restrict bacterial biofilm formation. The YF₃ NP-coated catheters were able to significantly reduce bacterial colonization compared to the uncoated surface. Taken together, our results highlight the potential to further develop the concept of utilizing these metal fluoride NPs as novel antimicrobial and antibiofilm agents, taking advantage of their low solubility and providing extended protection.