BackgroundNurses' clinical education is critical in their empowerment process. Due to the extraordinary sensitivity of special wards, nurse training, especially for novices, appears to be more necessary and critical. The present study aimed at determining how triple-lumen flushing training based on the guideline affected the capacity of nurses in Namazi Hospital's pediatric intensive care unit.Methods The current study was a quasi-experimental pre-test-post-test study conducted in December 2020 until April 2021 on 60 nurses working in the pediatric intensive care units of Namazi Hospital in Shiraz. The samples were counted and divided into two groups of 25 people using the census method. At the beginning of the study, all participants took a pre-test, and then one of the groups was chosen randomly and trained for 10 one-hour sessions based on the revised guidelines of Shiraz University of Medical Sciences professors of Nursing and Cardiology. The training was both theoretical and practical in nature. A four-choice test, a performance checklist, and a valid and reliable attitude questionnaire were used to evaluate the effect of empowerment training in changing the behavior of both intervention and control groups after two weeks. Data were analyzed by SPSS software version 23 using descriptive and inferential statistical methods.Results Data analysis revealed a statistically significant difference in knowledge, skills, and attitudes between the intervention and control groups, with a statistically significant coefficient (p 0.000). There is a positive and significant correlation between nurses' clinical knowledge and their clinical skills (r = 0.290, p = 0.041). In other words, nurses' clinical skills have improved in parallel with their clinical knowledge. Furthermore, there is no significant correlation between nurses' attitudes and their level of clinical knowledge (r=0.066, p = 0.650). After the intervention, there is no significant correlation between nurses' attitudes and their level of clinical skills (r=0.030, p= 0.836).Conclusion The current study's findings revealed that the educational intervention of triple-lumen flushing based on the designed guideline has significantly contributed to the excellence and promotion of knowledge, and as a result, the ability of nurses. Developing and implementing guidelines can improve nurses' abilities in specialized areas, particularly in special care.