Background: Critically ill patients experience a variety of distressing symptoms during their intensive care stay including pain, agitation, delirium, weakness, and sleep deprivation. Because of the complexity of caring for those patients, these symptoms are often managed by the “ABCDEF" bundle that improves intensive care unit outcomes.Aim: Evaluatethe impact of “ABCDEF" bundle application on nurses' performance and patients' outcomes in critical care units. Design: A quasi-experimental design (pre/posttest for nurses and study/control for patients) wereutilized to evaluatethe impact of “ABCDEF" bundle application on nurses' performance and patients' outcomes in critical care units.Setting: The study wasperformed at medicine ICU affiliated to Ain Shams University Hospitals, Cairo. Egypt. Subjects: A convenient sample of all available nurses (30) working at medicine ICU &A purposive sample of (50) adult patients from both gender andfree from mental disability recruited to this study from the previous mentioned setting.Tools: Tool (I) Nurses self-administered structured knowledge questionnaire, Tool (II) Nurses' practice observational checklist & Tool (III): Patients outcomes assessment record. Results: showed that there was an obvious statisticalenhancement in the studied nurses' total satisfactory level of knowledge and practice immediate and post implementation of“ABCDEF" bundle applicationat p˂0.05, in addition to there was statistically significant improvement in patients'outcomes in the study group rather than the control group atp˂0.05 except for mortality rate.Conclusion: In view of the findings, the research hypothesis has been proved as the application of “ABCDEF" bundle has a positive effect on nurses' performance; as it improved their knowledge and practical level and consequently has a positive effect in refinement the outcomes for patients in the study group rather than the control group with a statistically significant difference.Recommendations:Conducting Inservice training programs regarding ABCDEF bundle application for nurses caring of patients in the intensive care unit.