In an effort to identify process failures related to infectious disease spread in hospital settings, the authors analyzed patient safety events related to viruses and bacteria spread through respiratory droplets (e.g., pertussis, meningitis, measles) reported to the Pennsylvania Patient Safety Reporting System over a 12-month period. The analysis identified several process failures, most commonly involving the testing or processing of laboratory specimens and isolation-related procedures. The authors also discuss risk-reduction strategies to reduce the process failures contributing to the spread of infectious disease. These findings can assist organizations to develop strategies to reduce infection disease risk, which is important during the ongoing COVID-19 pandemic.