Background: A growing body of evidence implicates subclinical (biofilm) infection around breast implants as an important cause of capsular contracture (CC). Objectives: The authors use an in vivo porcine model to investigate the potential of antibiotic-impregnated mesh as a prophylactic measure against biofilm formation and CC. Methods: A total of 28 implants (14 untreated controls, 14 treated with antibiotic mesh) were inserted into 5 adult female pigs. All implants and pockets were inoculated with a human clinical strain of Staphylococcus epidermidis. The implants were left in situ for 16 weeks and then analyzed for contracture using both Baker grading and applanation tonometry. The presence of biofilm infection was assessed by subsequent microbiological analysis of implants and capsules. Results: One untreated implant had extruded and was excluded from analysis. The tissue surrounding the 13 untreated control implants had Baker Grade III/IV CC, whereas no CC was identified around the 14 antibiotic mesh-treated implants. This difference was highly significant (P < .001). Tonometry findings were consistent with the Baker assessments. Although bacterial biofilm was detected on all implants and capsules, the biofilms on the antibiotic-treated implants and surrounding capsules were generally single-layered or isolated in contrast to the multilayer biofilms found on untreated implants and capsules. Conclusions: Based on the findings from this study of a porcine model, the use of antibiotic-impregnated mesh reduces bacterial access to breast implants at the time of surgical insertion and may subsequently protect against subclinical infection and CC.