Tibial plateau leveling osteotomy (TPLO) is one of the most common surgical techniques performed to stabilize a cranial cruciate insufficient stifle in dogs. Although it is classified as a clean surgical procedure, it is associated with a high surgical site infection (SSI) rate. Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is the predominant pathogen causing TPLO SSI and is difficult to treat because of its multi-drug resistance. This thesis is an investigation into the use of perioperative antimicrobial prophylaxis and factors associated with SSI occurrence following TPLO in dogs, including MRSP carriage. We identified that perioperative antimicrobial prophylaxis protocols are not being administered appropriately, however, failure of adherence to these protocols was not associated with SSI. Furthermore, preoperative MRSP carriage was a risk factor and postoperative antimicrobial use was protective against the occurrence of TPLO SSI. Further study into the factors associated with TPLO SSI is required to understand this clinically important challenge.