We reviewed trimethoprim-sulfamethoxazole antibiotic susceptibility testing data among Staphylococcus aureus using 3 national inpatient databases. In all 3 databases, we observed an increases in the percentage of methicillin-resistant Staphylococcus aureus that were not susceptible to trimethoprim-sulfamethoxazole. Providers should select antibiotic regimens based on local resistance patterns and should report changes to the public health department.