After Food and Drug Administration (FDA) approval of premixed antibiotic bone cements (polymethylmethacrylate [PMMA]), these products are being used with increasing frequency during revision and primary hip and knee arthroplasties. To date, no studies have compared the antimicrobial efficacy of more than 2 products directly. Using a 7-day modified Kirby-Bauer assay, we assessed the in vitro antibacterial properties of 5 FDA-approved, commercially available antibiotic PMMAs. Significant differences in antimicrobial activity were noted among the antibiotic PMMA products included in this investigation. Antibacterial activity of all products tested was greatest on day 1 and rapidly diminished thereafter. Results of this investigation suggest that the antibacterial efficacies of premixed antibiotic PMMA products are not equivalent.