Health care–associated infections remain one of the most common preventable adverse events in hospitals, despite some successes at reducing rates of specific infections. Preventing infections caused by methicillin-resistant Staphylococcus aureus (MRSA) remains a difficult problem, as studies of prevention techniques have reached conflicting results. This large-scale study of an MRSA prevention bundle implemented in the Veterans Affairs system found that a multifaceted approach including universal screening, contact isolation precautions, and an emphasis on infection control as part of safety culture resulted in a significant reduction in MRSA infections in both intensive care and ward patients. Although the overall incidence of hospital-acquired MRSA infections has been decreasing nationwide, the effects of these infections can be devastating—as vividly described in this AHRQ WebM&M commentary.