Background: Endotracheal tube suctioning (ETS) is a crucial procedure that neonatal and pediatric nurses should perform in effective and efficient way through exposure to various teaching methods such as simulation and periodic training. Aim: to investigate effect of using instructional module (IM) versus simulation based endotracheal suction education on the performance and self-efficacy of Neonatal Intensive Care Unit (NICU) nurses. Research design: Quasi-experimental research design. Sample: all nurses working in the NICU (50) nurses at the time of data. Setting: Tanta University hospital. Tools: Tool 1: Nurses' Knowledge regarding endotracheal tube suctioning, Tool 2: Endotracheal Suction Observation Checklist and Tool 3: General Self-efficacy Scale. Results: levels and total mean scores of nurses' knowledge, practice, and self-efficacy about ETS were found to have significantly improved before, after, and eight weeks after the teaching intervention. Conclusion: Both methods were beneficial in enhancing nurses' knowledge, practice and self-efficacy in performing ETS but differences were higher in the total levels and mean scores among nurses who received simulation-based education. Recommendations: periodic and continuously supervised training should be provided for (NICU) nurses regarding ETS to improve the patient's outcome.