The purpose of this study was to examine the association between rates of methicillin-resistant Staphylococcus aureus (MRSA)/ Clostridioides difficile and quality and clinical outcomes in US acute care hospitals. The population was all Medicare-certified US acute care hospitals with MRSA/ C difficile standardized infection ratio (SIR) data available from 2013 to 2017. Hospital-level data from the Centers for Medicare & Medicaid Services were used to estimate hospital and time fixed effects models for 30-day hospital readmissions, length of stay, 30-day mortality, and days in the intensive care unit. The key explanatory variables were SIR for MRSA and C difficile. No association was found between MRSA or C difficile rates and any of the 4 outcomes. The null results add to the mixed evidence in the field, but there are likely residual confounding factors. Future research should use larger samples of patient-level data and appropriate methods to provide evidence to guide efforts to tackle antimicrobial resistance.