Healthcare Failure Mode and Effects Analysis (HFMEA) is a methodology for correcting latent system errors before they lead to adverse events. We examined the utility of HFMEA in evaluating the sterilization and use of surgical instruments. First, a multidisciplinary team graphed the process in a flow diagram. A hazard analysis was then used to examine potential failure modes (i.e., ways in which a process can fail) and their causes and to score the severity and other factors for each failure mode cause. Actions were then planned to address the selected failure mode causes. Flow charts were created for 3 foci: sterilization process, reading of biologicals, and use of equipment. Information was gathered through interviews and a review of the literature. Multiple clinically significant system errors were identified, and actions to correct them were developed. The HFMEA methodology facilitated the detection of previously unrecognized system errors, demonstrating its potential utility in addressing healthcare epidemiology-related adverse events.