Background: Peripheral intravenous (PIV) infiltration and extravasation are common complications of intravenous fluid administration. Here, we aim to investigate risk factors associated with major adverse events following PIV infiltration, which may help risk stratify those who require early surgical consultation. Methods: Retrospectively, patients were identified who had a documented PIV infiltration or extravasation event at 3 academic hospitals between 2015 and 2022. A major adverse advent was defined as a full-thickness injury requiring operative management (deep infection, compartment syndrome). A minor adverse event was defined as superficial injury (cellulitis, superficial thrombosis). Results: In total, 160 patients with PIV infiltration events were included (37.5% men), with an average age of 64.1 years. A surgical consult for a hand specialist was placed 35% of the time: orthopedic surgery in 46.4% of cases and plastic surgery in 42.9%. Among these consults, 87.5% recommended supportive treatment (elevation, warm/cold compresses, serial examinations). Major adverse events occurred in 4.4% (n = 7) of patients, and minor adverse events occurred in 11.3% (n = 18). Both intensive care unit (ICU) admission and current intubation status (ie, intubated, sedated, and nonexaminable) at the time of infiltration were significantly associated with adverse events ( P = .02 and P = .03, respectively). Current intubation status was significantly associated with operative management ( P = .001). Conclusion: Robust characterization of PIV infiltration events may facilitate early identification of patients at risk of serious complications. We found ICU admission and current intubation both to be associated with adverse events following PIV infiltration. Further work should be done to evaluate the risk of infiltration with different fluid types (vesicant, nonvesicant).