Infection of implanted medical devices is a major clinical complication that affects millions of people worldwide and costs 5-10 billion dollars per year to treat. Most infections involve biofilms that are resistant to antibiotics, as they often cannot penetrate biofilm formations. Therefore, new biomaterials are needed to reduce or eliminate microbial adhesion and infections of medical devices. When looking for biomaterial nanoparticles, along with their antimicrobial properties, we also have to consider their toxicity. Magnesium oxide nanoparticles (nMgO) have antimicrobial activity and can be metabolized and fully reabsorbed in the body. nMgO has been shown to kill both planktonic bacteria and disturb nascent biofilm. We hypothesize that the action mechanisms of nMgO against planktonic bacteria can be integrated into medical devices to evoke antimicrobial responses without harming host cells. Previously, the minimum bactericidal concentration (MBC) was determined for Escherichia coli (E. coli). To benefit from the antimicrobial properties of nMgO, we need to determine whether E. coli develops resistance when repeatedly exposed to develop resistance to nMgO exposure. Here, we used spectrophotometry to measure the growth of Gram-negative E. coli after exposure to nMgO. After testing the efficacy of MgO nanoparticles on E. coli, we determined that there was a reduction in bacterial growth, indicating a resistance mechanism. It is anticipated that the results of this study will be used in downstream clinical applications and orthopedic device implantations.