The purpose of this study was to compare 1) the load and diversity of cultivatable species of bacteria isolated from tissue biopsies with culture of surface swabs, and 2) the ability of each technique to detect methicillin-resistant Staphylococcus aureus (MRSA) in a model of MRSA-infected equine wounds. Four 2.5 x 2.5 cm full-thickness skin wounds were created on the dorsolateral aspect of each forelimb. Five days later, each wound was inoculated with differing amounts of MRSA (ATCC® 43300™). Surface swab (Levine technique) and tissue biopsy samples (3 mm punch biopsy) were obtained at 2-,7-,14-, and 21-days post-inoculation. Quantitative aerobic culture was performed using routine clinical techniques. A similar bacterial profile was identified from cultures of each wound sampling technique and there was moderate correlation (R = 0.49, P <0.001) of bacterial bioburden. There was fair agreement (kappa = 0.31; 95% CI, 0.129 to 0.505) between the sampling techniques in terms of identification of MRSA. MRSA was isolated significantly (P=0.016) more frequently from cultures of tissue biopsies (79%; 76/96) than from surface swabs (62%; 60/96). Both wound sampling techniques reveal similar information about bacterial load and diversity, but MRSA is detected more often from cultures of tissue biopsies. Limitations included small sample size and use of only aerobic cultures. Understanding the differences between wound sampling techniques is important because identification of antimicrobial resistant bacteria has implications for management decisions in complex equine wounds.