Antibiotic-induced hemolytic anemia is a rare complication. Prophylactic cephalosporins are widely used in patients having orthopaedic procedures. When there is a precipitous drop in hemoglobin levels, it is important for the clinician to consider the possibility of drug-induced anemia when other causes of blood loss have been excluded. We present a patient with no prior drug allergies who had antibiotic-induced hemolytic anemia develop after total knee arthroplasty.