In the face of emerging multidrug-resistant microbes, reliable animal models are needed to study potential new therapies in infected wounds. To this end, we implanted screw-top titanium chambers subdermally in full-thickness wounds on both flanks (n = 6 per flank) of 2 Goettinger minipigs. After 1 wk, chambers were inoculated with Staphylococcus aureus, Pseudomonas aeruginosa, or vehicle only. Throughout the study, wound fluid was harvested for quantitative bacterial cultures to monitor infection. Animals were followed for 4 wk, after which tissue biopsies were taken for histologic analysis and quantitative bacterial counts. The implanted titanium chambers were well tolerated by the pigs throughout the study. After inoculation of the chambers, wound infection was established and maintained for 14 d. Despite infection, no systemic effects were noted. Cross-contamination was negligible, compared with the vehicle-only control. After tissue ingrowth, each chamber creates a closed system that allows harvest of exudate or application of substances without loss of material from the chamber. Because 12 chambers are implanted in each pig, researchers have the opportunity to compare multiple treatment options (for example, antibiotics, antimicrobial peptides, gene therapy) in the same animal, with no interindividual variation. We conclude that the use of titanium chambers in pigs provides a reliable and reproducible in vivo model to investigate wound healing, wound infection, and treatment options.