We report a case of a surgical site infection caused by clindamycin-susceptible, erythromycin-resistant methicillin-resistant Staphylococcus aureus (MRSA) that did not respond to treatment with clindamycin. The MRSA isolate obtained after treatment was resistant to clindamycin but was found to be identical by pulsed-field gel electrophoresis to the clindamycin-susceptible isolate obtained before treatment. A post hoc erythromycin-induction test (D test) confirmed the presence of in vitro inducible macrolide-lincosamide-streptogramin B resistance (iMLS) in the pretreatment isolate. Erythromycin induction testing confirmed in vitro iMLS in 90 (56%) of 161 erythromycin-resistant, clindamycin-susceptible clinical S. aureus isolates overall and in a significantly higher proportion (78%) of methicillin-susceptible S. aureus isolates from pediatric patients. Our clinical laboratory currently tests all S. aureus isolates for iMLS before reporting clindamycin susceptibility.