We report pH/bacteria-responsive nanocomposite coatings with multiple mechanisms of antibacterial protection that include the permanent retention of antimicrobials, bacteria-triggered release of antibiotics and bacteria-induced film swelling. A novel small-molecule-hosting film was constructed using layer-by-layer deposition of montmorillonite (MMT) clay nanoplatelets and polyacrylic acid (PAA) components, both of which carry a negative charge at neutral pH. The films were highly swollen in water, and they exhibited major changes in swelling as a function of pH. Under physiologic conditions (pH 7.5, 0.2 M NaCl), hydrogel-like MMT/PAA films took up and sequestered ∼45% of the dry film matrix mass of the antibiotic gentamicin, causing dramatic film deswelling. Gentamicin remained sequestrated within the films for months under physiologic conditions and therefore did not contribute to the development of antibiotic resistance. When challenged with bacteria (Staphylococcus aureus, Staphylococcus epidermidis or Escherichia coli), the coatings released PAA-bound gentamicin because of bacteria-induced acidification of the immediate environment, whereas gentamicin adsorbed to MMT nanoplatelets remained bound within the coating, affording sustained antibacterial protection. Moreover, an increase in film swelling after gentamicin release further hindered bacterial adhesion. These multiple bacteria-triggered responses, together with nontoxicity to tissue cells, make these coatings promising candidates for protecting biomaterial implants and devices against bacterial colonization. A thin film coating for medical implants and other biomedical devices can be triggered to fight bacterial infection when required. Svetlana Sukhishvili of Stevens Institute of Technology in the United States and collaborators in Kazakhstan and the Netherlands developed the film, which is composed of montmorillonite clay nanoplatelets and polyacrylic acid. The film can take up and retain the antibiotic gentamycin at up to 45% of its dry mass. When bacteria adhere to the film, the antibiotic is released and the film swells to prevent bacterial penetration. Some antibiotic remains bound within the film, offering lasting antibacterial protection. The system is less likely to promote antibiotic resistance than routine antibiotic use as its effects are triggered only if a significant bacterial challenge occurs. It could also be adapted to carry a variety of other antibiotics. Antimicrobial-containing nanocomposite coatings can respond to bacterial challenge through multiple mechanisms and show unprecedented antibacterial efficacy. Coatings composed of similarly charged montmorillonite (MMT) clay nanoplatelets and polyacrylic acid (PAA) can take up and sequester large amounts of antibiotics under normal physiologic conditions, preventing the development of antibiotic resistance. When challenged with media-acidifying bacteria (Staphylococcus aureus, Staphylococcus epidermidis or Escherichia coli), they release PAA-bound gentamicin and increase their water uptake, while retaining MMT-bound antibiotics. These multiple bacteria-triggered responses, together with biocompatibility to tissue cells, make these coatings promising candidates for protecting biomaterial implants and devices against bacterial colonization.