Purpose: This study investigated the knowledge, attitudes, and perceptions of a safe environment, as well as self-reported and observed compliance with the use of personal protective equipment (PPE), among intensive care unit (ICU) nurses. Methods: This study was conducted in October 2021 with 55 nurses working in the medical and surgical ICUs of a general hospital in Seoul. A self-reported questionnaire and an observational tool for compliance with the use of PPE were used to collect data. Results: Except for masks, the observed compliance for all other PPE types was lower than the self-reported compliance. Male nurses showed significantly higher observed compliance than female nurses. Self-reported compliance with PPE use, including “when there is a possibility of contact with objects contaminated with blood or body fluids, mucous membranes, damaged skin, or contaminated skin” (r = .23, p = .015) and “when there is a possibility of contact with blood, body fluids, secretions, or exudates” (r = .27, p = .004) showed significant correlations with knowledge of PPE. In the results for self-reported compliance with PPE use, gown use had a significant correlation with knowledge (r = .24, p < .001) and perceptions of a safe environment (r = .15, p = .016) for PPE, and gloves showed significant correlations with attitudes (r = .14, p = .024) and perceptions of a safe environment (r = .18, p = .003). Conclusion: The observed compliance with PPE use tended to be lower than the self-reported compliance among ICU nurses. It is necessary to develop and apply an effective educational program that can enhance improve actual compliance with PPE use among intensive care unit nurses.