Antibiotic-loaded bone cement (ALBC) spacers are the mainstay in 2-stage revision, but antibiotics (vancomycin plus aminoglycosides) may undergo systemic absorption, resulting in acute kidney injury (AKI). Data on spacer antibiotics are heterogeneous. Our objective was to review risk factors for AKI and dosage of antibiotics. Significant AKI risk factors were antibiotic concentration greater than 3 or 3.6 g per cement batch, comorbidities, chronic kidney disease, and hypovolemia. Despite similar spacer antibiotic dosing, there was remarkable variability in serum concentrations. To err on the side of caution, it appears that antibiotic dose below 3 g per cement batch might be relatively safe until more evidence surfaces. Consideration of risk factors for AKI calls for appropriate antibiotic use in 2-stage revision. [Orthopedics. 2023;46(3):e136-e142.].