Background: A safety checklist is useful in the hemodialysis unit, as it can keep nurse focused and preventing mistakes under pressure. Aim: This study evaluates the effect of implementing safety guidelines on nurses‘ performance and safety parameters for adolescents & young adults undergoing hemodialysis. Design: A quasiexperimental design using one group pre-posttest. Setting: the research was conducted in the hemodialysis units at Mansoura University Children's Hospital and Ain-shams University Hospitals in Egypt. A total sample size of 80 nurses was recruited, 40 nurse from each setting and purposive sample of (41) adolescents and (41) young adults who fulfilling the inclusion and exclusion criteria. Three tools were used for data collection: nurses' knowledge regarding safety guidelines during hemodialysis questionnaire; Hemo Pause safety assessment observational checklist and hemodialysis Patient safety parameters questionnaire. Results: There are improvements in nurses‘ knowledge as evidenced by 70% and 82.5% of nurses had good knowledge and 97.5 and 80% of them had competent practice in both hospitals after implementing safety guidelines and Hemo-Pause checklist. Additionally, half of patients had high safety parameters in post intervention phase than in pre intervention which statistically significant difference at (p≤ 0.001). Conclusion: this study highlights the positive impact of implementing safety guidelines and utilizing the Hemo-Pause checklist on nursing practice and safety parameters in hemodialysis for adolescents and young adults. Recommendation: continuous training and educational programs should be provided to enhance nurses‘ performance regarding patient safety and the use of checklists to enhance nurses' performance in providing safe and efficient care.