Background: There are a two-system suction of the endotracheal, in which a closed-system suction improves oxygen desaturation by decreasing the lung tidal volume compared to an open-system suction. Most nurses' practices are unobserved and require improvement in those critical practices. Aim: This study aimed to compare the performance level of critical care nurses toward two systems of endotracheal suction among mechanically ventilated patients. Subject and Methods: A cross-sectional comparative research design study was conducted at adult critical care units at Suez Canal University hospitals in Ismailia city. They were sorted into two groups by random selection: group (I) included 32 nurses for whom open suction was utilized, while group (II) included 32 nurses for whom closed suction was utilized. Utilizing self-administered questionnaires to assess nurses' demographic features and level of knowledge, self-efficacy, and observational checklists to assess nurses' practice. Results: There was a highly statistically significant difference between the performance of critical care nurses in open and closed system suction (68%; 47%) consecutively. However, there was a statistically significant correlation in both groups with age, educational level, and experience year. Conclusions: More of those studied nurses had a technical institute in both study groups. Also, there is an overall difference in satisfactory performance levels between open endotracheal suction group I and closed endotracheal suction group II. Recommendations: In-service-led continuous training courses improve nurses' performance in the closed suction system and upgrade open suction. Critical care nurses ought to be attentive sequentially to the use of the suction system and updated nursing guidelines in regular practice. Further replication of the study in all intensive care units in the aforementioned setting is needed for data generalization.