Anesthetics and adjunct agents have a long history of being associated with patients engaging in delirious or agitated behavior in a perioperative setting. Prior to this study, few have explored the topic with a focus on safety for both the patient and staff. We explored the Pennsylvania Patient Safety Reporting System (PA-PSRS) database for event reports to identify bouts of delirium/ agitation associated with anesthetics and/or adjunct agents that occurred during the pre-, intra-, or postoperative period. We identified 97 event reports from 63 healthcare facilities over a two-year period. Patients’ ages ranged from 1 to 91 years and 66% of the patients were reported as male. Also, 8% of the delirium/agitation occurred preoperatively, 8% intraoperatively, and 84% postoperatively. Across all three operative periods, 62% of the reports described dangerous/nonviolent behavior and 26% described dangerous/violent behavior. Additionally, 40% of the event reports described one or more patient injuries (e.g., cardiopulmonary arrest, asphyxiation, hematoma, prolapse/dehiscence, progressive ischemia) and 36% of the patients required additional healthcare services or monitoring (e.g., intra- or interfacility transfer, additional surgical procedure). Finally, 54% of the event reports described patient behavior that created an immediate and high risk of staff harm. Overall, the current study provides novel insight into how delirium/agitation has varying safety implications depending on the operative period. We encourage readers to review Table 5, which proposes a four-phase intervention package to prevent, treat, and de-escalate bouts of delirium/agitation.