Full-thickness excision wounds infected with Staphylococcus hyicus, a pig pathogen, or Staphylococcus aureus, a human pathogen, were produced in pigs. The inoculated wounds were kept occluded for 2 days and then exposed and biopsied at intervals for 9 to 12 days. The exposed lesions were edematous and exudative. The S. aureus model was experimentally advantageous because the infection remained localized to the wound without systemic infection or signs of discomfort. The S. hyicus infection caused a rash with skin blisters; thus, its use is discouraged. The concentration of S. hyicus in the wound on day 2 was log 8.6 ± 0.4 CFU/g (mean ± standard deviation). On day 4 the mean was log 9.2. For S. aureus the values were log 8.0 ± 0.9 on day 2 and 6.9 on day 4 (p < 0.05). Of the 50 individual values in the S. aureus series, 45 were above log 5. The inflammatory reaction was more pronounced after the infection with S. hyicus, whereas with S. aureus the fibroblast response came earlier and was more pronounced. The model parallels typical clinical courses of staphylococcal infection.