This is a prospective, single-center, open-label study evaluating systemic vancomycin levels following preoperative intraosseous administration in patients undergoing primary unilateral total knee arthroplasty. Eligible participants will receive preoperative intraosseous vancomycin (500 mg in 100 mL saline) as part of standard perioperative infection prophylaxis. The study is open-label due to the nature of the intervention. Blood samples will be collected at predefined time points intraoperatively to measure serum vancomycin concentrations. Patients will be randomized to either a tourniquet or no tourniquet for these blood draws.

Inclusion Criteria:

1. Is a patient over the age of 18 receiving treatment at UC San Diego
2. Is undergoing primary unilateral total knee arthroplasty
3. Is able to provide consent
4. Is candidate for IO administration of Vancomycin

Exclusion Criteria:

1. Has had a previous surgery on the knee of interest (with the exception of arthroscopy)
2. Has a BMI >35
3. Has a contraindication to receiving vancomycin, cefepime, or cefazolin (i.e. allergy)
4. Has diabetes with A1c >7.5% (unless with controlled fructosamine)
5. Is immunocompromised/immunosuppressed (i.e. due to HIV, hepatitis C, end-stage renal disease, post-transplant status, chemotherapy or radiation therapy within 6 months of surgery, immunomodulating medications)
6. Has a history of active infection
7. Inability to provide consent
8. Prisoner
9. Pregnant women