Periprosthetic joint infections (PJI) are a common reason for orthopedic revision surgeries. It has been shown that the silver surface modification of a titanium alloy (Ti–6Al–4V) by PMEDM (powder mixed electrical discharge machining) exhibits an antibacterial effect on Staphylococcus spp. adhesion. Whether the thickness of the silver-modified surface influences the adhesion and proliferation of bacteria as well as the ossification processes and in-vivo antibacterial capacity has not been investigated before. Therefore, the aim of this work is to investigate the antibacterial effect as well as the in vitro ossification process depending on the thickness of PMEDM silver modified surfaces.The attachment of S. aureus on the PMEDM modified surfaces was significantly lower than on comparative control samples, independently of the tested surface properties. Bacterial proliferation, however, was not affected by the silver content in the surface layer. We observed a long-term effect of antibacterial capacity in vitro, as well as in vivo. An induction of ROS, as indicator for oxidative stress, was observed in the bacteria, but not in osteoblast-like cells. No influence on the in vitro osteoblast function was observed, whereas osteoclast formation was drastically reduced on the silver surface. No changes in cell death, the metabolic activity and oxidative stress was measured in osteoblasts.We show that already small amounts of silver exhibit a significant antibacterial capacity while not influencing the osteoblast function. Therefore, PMEDM using silver nano-powder admixed to the dielectric represents a promising technology to shape and concurrently modify implant surfaces to reduce infections while at the same time optimizing bone ingrowth of endoprosthesis.