Bacteria that adhere to the surfaces of implanted medical devices can cause catastrophic infection. Since chemical modifications of materials' surfaces have poor long-term performance in preventing bacterial buildup, approaches using bactericidal physical surface topography have been investigated. The authors used Nanoimprint Lithography was used to fabricate a library of biomimetic nanopillars on the surfaces of poly(methyl methacrylate) (PMMA) films. After incubation of Escherichia coli (E. coli) on the structured PMMA surfaces, pillared surfaces were found to have lower densities of adherent cells compared to flat films (67%-91% of densities on flat films). Moreover, of the E. coli that did adhere a greater fraction of them were dead on pillared surfaces (16%-141% higher dead fraction than on flat films). Smaller more closely spaced nanopillars had better performance. The smallest most closely spaced nanopillars were found to reduce the bacterial load in contaminated aqueous suspensions by 50% over a 24-h period compared to flat controls. Through quantitative analysis of cell orientation data, it was determined that the minimum threshold for optimal nanopillar spacing is between 130 and 380 nm. Measurements of bacterial cell length indicate that nanopillars adversely affect E. coli morphology, eliciting a filamentous response. Taken together, this work shows that imprinted polymer nanostructures with precisely defined geometries can kill bacteria without any chemical modifications. These results effectively translate bactericidal nanopillar topographies to PMMA, an important polymer used for medical devices.